Molecular Imaging - archive.rsna.org

MolecularImagingProgram subject to change until 12/16/2019.

MI001-EB-X

Role of Imaging in Treatment Response Evaluation of Chimeric Antigen Receptor (CAR) T Cell Therapy inPatients with Diffuse Large B-Cell Lymphoma (DLBCL)

All Day Room: MI Community, Learning Center Hardcopy Backboard

ParticipantsReza Sirous, MD,MPH, Baltimore, MD (Presenter) Nothing to DiscloseRaheleh Taghvaei, MD, Philadelphia, PA (Abstract Co-Author) Nothing to DiscloseVivek Kesari, MD, Columbia, MD (Abstract Co-Author) Nothing to DiscloseBabak Saboury, MD, MPH, Baltimore, MD (Abstract Co-Author) Nothing to Disclose

For information about this presentation, contact:

[email protected]

TEACHING POINTS

1-What is CAR T Cell therapy & importance of reliable follow up?2-Compare imaging vs. non-imaging techniques (e.g. liquid & tissuebiopsy) in following up post CAR T cell patients.3-Compare labeling/radiolabeling vs. reporter genes as the 2 main investigationalapproaches for following up post CAR T Cell patients: pitfalls & advantages.4-Compare different imaging modalities, such as MRI,molecular imaging (SPECT, PET), Bioluminescence imaging in following up post CAR T-Cell patients: advantages & pitfalls.5-Overview of PET/CT imaging in patients post CAR T-Cell.6-How to interpret 18F-FDG PET/CT in patients post CAR T-Cell therapyfor: pearls and pitfalls.

TABLE OF CONTENTS/OUTLINE

1-CAR T Cell therapy: a-Technique b-Application in DLBCL c-Side effects d-Significance of follow up 2-Non-imaging vs. imagingfollow up techniques: a-Advantages b-Pitfalls 3-Labeling/radiolabeling vs. reporter genes: a-what is a reporter gene? b-what islabeling? c-advantages & pitfalls of each method 4-Different modalities in following up post CAR T Cell therapy: a-MRI: advantages,pitfalls b-CT: advantages, pitfalls c-PET: different tracers, advantages, pitfalls d-Bioluminescence imaging: advantages, pitfalls 5-Pearls and pitfalls of 18F-FDG PET/CT imaging post CAR T Cell: a pictorial review of treatment response evaluation.6-Future ofimaging in cell trafficking & summary.

Printed on: 10/29/20

MI002-EB-X

The Nuclear Radiologist's GPS of the Neck: The Neighborhoods of Lymph Nodes, Spaces, and Anatomical LandMarks by PET/CT and Multiple Imaging Modalities


ParticipantsNael M. Khayyat, MD, Burr Ridge, IL (Presenter) Nothing to DiscloseAmanda B. Allen, DO, Chicago, IL (Abstract Co-Author) Nothing to DiscloseThomas M. Anderson, MD, Chicago, IL (Abstract Co-Author) Nothing to Disclose

TEACHING POINTS

To show landmarks of head and neck normal anatomy..


FDG PET/CT reading in H&N can be quite challenging due to the lack of anatomic landmarks by PET and the variable physiologicvariation of FDG uptake. There is a considerable physiologic variation of FDG uptake that can be visualized before and aftertreatment. After viewing the exhibition, PET/CT interpreters should be able to recognize anatomical landmarks of the Head and Neckduring PET/CT interpretation with the correlation of MRI and CT scans, recognize normal versus abnormal patterns of FDG uptake,recognize treatment changes and artifacts. The reader also should recognize the regional lymph nodes classification as it isessential in staging and restaging. PET/CT images are presented to provide examples of variable regional lymph nodes and spaces.Examples of benign activity and artifacts are included with correlation to the anatomical landmarks, such as lymphoid tissue (tonsilsand adenoids), salivary glands, soft palate, tongue, hard palate, alveolar ridge, retromolar trigon, brown fat, muscle activity,Examples of how to recognize landmarks and borders of the surgical neck lymph nodes levels are included as well.


MI003-EB-X

Spotlight on Clinical PET/MR: Colorectal Cancer - All You Need to Know


ParticipantsAlexander J. Herold, Vienna, Austria (Abstract Co-Author) Nothing to DiscloseBarbara Amorim, Campinas, Brazil (Abstract Co-Author) Nothing to DiscloseShadi Abdar Esfahani, MD,MPH, Boston, MA (Abstract Co-Author) Nothing to DiscloseVinay Prabhu, MD, Boston, MA (Abstract Co-Author) Nothing to DiscloseDebra A. Gervais, MD, Boston, MA (Abstract Co-Author) Nothing to DiscloseDavid Groshar, MD, Petah Tikva, Israel (Abstract Co-Author) Nothing to DiscloseLale Umutlu, MD, Essen, Germany (Abstract Co-Author) Consultant, Bayer AGCiprian Catana, MD, PhD, Charlestown, MA (Abstract Co-Author) Nothing to DiscloseUmar Mahmood, MD,PhD, Charlestown, MA (Abstract Co-Author) Co-founder, CytoSite Biopharma; Shareholder, CytoSite Biopharma;Consultant, CytoSite Biopharma; Grant, CytoSite Biopharma; ; ; Bruce R. Rosen, MD, PhD, Charlestown, MA (Abstract Co-Author) Nothing to DiscloseSarah Poetter-Lang, Vienna, Austria (Abstract Co-Author) Nothing to DiscloseOnofrio A. Catalano, MD, Boston, MA (Presenter) Nothing to DiscloseMarius E. Mayerhoefer, MD,PhD, Vienna, Austria (Abstract Co-Author) Speaker, Siemens AG; Research support, Siemens AG


[email protected]

TEACHING POINTS

The purpose of this exhibit is: 1. To review the technical and physical fundamentals of PET/MR 2. To discuss the current status ofPET/MR in initial staging as well as follow up of colorectal cancer (CRC) 3. To elucidate the pitfalls and strengths of PET/MR in CRCassessment


1. PET/MR - Imaging technology 2. CRC staging, clinical expectations and needs 3. Indications and contraindications to PET/MR 4.Patient preparation 5. Tailored PET/MR protocols 6. Current status of PET/MR: Review of the literature and of our personalexperience 7. Pitfalls of PET/MR and how to avoid them 8. Strengths of PET/MR 9. Future directions 10. Summary


MI004-EB-X

Demystifying Diffusion-Weighted MR Imaging: From Biophysical Basis to Evolving Imaging Biomarker


ParticipantsSimona Morochnik, PhD, Chicago, IL (Presenter) Nothing to DiscloseYu-hui Huang, MS, Chicago , IL (Abstract Co-Author) Nothing to DiscloseXiaohong J. Zhou, PhD, Chicago, IL (Abstract Co-Author) Owner, Medical Physics Services; Consultant, Horizon Medical PhysicsServices; Consultant, General Electric Company; Consultant, Rush University; Advisor, Chinese Academy of Sciences; Consultant,Chinese Academy of Sciences; Reviewer, American College of Radiology; Royalties, Reed ElsevierKaren Xie, DO, Chicago, IL (Abstract Co-Author) Nothing to Disclose

TEACHING POINTS

1. Although diffusion-weighted imaging (DWI) MRI has been routinely used in stroke and tumor evaluation, comprehensiveunderstanding of DWI techniques and evolving applications in oncology can be challenging to clinical radiologists. 2. We will describethe biophysical basis of DWI and review the relevant important technical aspects using simplified graphics to illustrate complexconcepts. 3. We will review emerging applications of DWI as a potential cancer biomarker for the detection, diagnosis,characterization, staging, and tumor response to therapy with examples of oncology imaging in breast, prostate, GI malignancy, andmultiple myeloma.


I. Biophysical Basis of DWI i. Water diffusion models: Gaussian vs. non-Gaussian; monoexponential vs. multiexponential; intravoxelincoherent motion (IVIM) ii. b-values: low to high iii. Apparent diffusion coefficient (ADC) and quantitative parameters iv. DWI incharacterization of tissue vascularity, cellularity, microstructure v. Technical challenges: signal to noise ratio, artifacts,standardization, reproducibility, validation II. DWI in Oncology i. Examples in Breast cancer Prostate cancer Hepatocellularcarcinoma GI malignancy Multiple myeloma ii. Cancer detection and diagnosis iii. Classification, grading, staging iv. Predicting andmonitoring treatment response v. Future development


MI005-EB-X

Circulating Tumor DNA (ctDNA) - A Potential Adjunct to FDG-PET Imaging in Cancer Follow Up


FDA Discussions may include off-label uses.

ParticipantsVidur Mahajan, MBBS, New Delhi, India (Presenter) Researcher, CARING; Associate Director, Mahajan Imaging; Researchcollaboration, General Electric Company ; Research collaboration, Koninklijke Philips NV; Research collaboration, Qure.ai; Researchcollaboration, Predible Health; Research collaboration, Oxipit.ai; Research collaboration, Synapsica; Research collaboration, QuibimShelly Mahajan, New Delhi, India (Abstract Co-Author) Nothing to Disclose


[email protected]

TEACHING POINTS

• With the continuous advances in healthcare - Next Generation Sequencing and PET-CT are revolutionising cancer diagnostics •Survival outcomes in cancer can be improved by early detection of metastatic disease or relapse during follow up • Next Generationsequencing is an extremely high end modality wherein hundreds to millions of DNA molecules are sequenced in parallel • CtDNA is anapplication of NGS to monitor the amount of tumor specific DNA in the peripheral blood of patient • Using ctDNA, a non-invasiveinvestigation, to monitor the remission status can potentially reduce the frequency of imaging required at follow up, hence reducingthe side effects and discomfort • According to Wong R et al, for colorectal cancer patients with indeterminate findings on routineinvestigations, ctDNA detection increases the probability that the findings indicate metastatic disease, including in a nonpredefinedsubset that also underwent FDG-PET imaging • Hence, using ctDNA as an adjunct to FDG-PET imaging during cancer follow-upseems to be an acceptable proposition


• What is ctDNA? How is it measured? • What are the current guidelines for cancer follow up? • Review of literature • Advantagesand limitations of FDG-PET imaging • Advantages and limitations of ctDNA • Conclusion • References


MI100-ED-X

Review of Ga-68 Dotatate PET/CT for Neuroendocrine Neoplasms: Atypical Sites of Metastasis and UnusualFindings

All Day Room: MI Community, Learning Center Digital Education Exhibit

ParticipantsRicardo Bello Martinez, MD, New York, NY (Presenter) Nothing to DiscloseSomali Gavane, MBBS, New York, NY (Abstract Co-Author) Nothing to DiscloseNasrin V. Ghesani, MBBS, New York, NY (Abstract Co-Author) Nothing to DiscloseAnthony R. Hafez, DO, New York, NY (Abstract Co-Author) Nothing to DiscloseYasir J. Ahmad, MBBS, New York, NY (Abstract Co-Author) Nothing to DiscloseSherif Heiba, MD, New York, NY (Abstract Co-Author) Nothing to DiscloseLale Kostakoglu, MD, MPH, New York, NY (Abstract Co-Author) Research Consultant, F. Hoffmann-La Roche Ltd


[email protected]

TEACHING POINTS

•Understand the biologic behavior and expected sites for midgut NET metastases•Understand the biologic behavior and expectedsites for PNET and lung NET metastases•Understand the atypical sites of NET metastases•Understand the unexpected unusualfindings


I. Neuroendocrine neoplasia A. Common locations: Gastrointestinal tract and the lungsII. 68Ga-DOTA-conjugated peptides. A.Unusual findings: degenerative osseous changes, inflammatory/infectious process, hemangioma, uncinate process, splenule,meningioma B. NENs metastasis 1. Midgut NET common sites of metastasis: liver, intraperitoneal, bones. 2. PNET and lung NETcommon metastasis: liver, nervous system, pleura, mediastinum. 3. Uncommon sites of metastasis: ovary, myocardial,intramuscular, breast, spinal cord, trachea.


MI101-ED-X

Not All that Glows is Prostate Cancer: False Positives in Ga68 PSMA PET CT for Prostate Cancer Imaging - APictorial Review


ParticipantsIndiresh N. Desai, MBBS, DMRD, Bangalore, India (Presenter) Nothing to DiscloseNikita K. Jain, MBBS,MD, Bangalore, India (Abstract Co-Author) Nothing to DiscloseShivakumar Swamy Shivalingappa, DMRD,MBBS, Bangalore, India (Abstract Co-Author) Nothing to DiscloseMahesh Ashok Kumar, MD,MBBS, Bangalore, India (Abstract Co-Author) Nothing to DiscloseKumar Kallur, MBBS, MD, Bangalore , India (Abstract Co-Author) Nothing to DiscloseAvinash R. Kesari, Bangalore , India (Abstract Co-Author) Nothing to DiscloseSudhakar Sampangi, DMRD, Bangalore, India (Abstract Co-Author) Nothing to DiscloseYashaswini K. Kumaraswamy, Bangalore , India (Abstract Co-Author) Nothing to DisclosePrashanth G.R, Bangalore, India (Abstract Co-Author) Nothing to DiscloseRajkumar K, Bangalore , India (Abstract Co-Author) Nothing to Disclose


[email protected]

TEACHING POINTS

The discovery and introduction of prostate-specific membrane antigen (PSMA) tracer has revolutionized the prostatic cancerimaging and management. However as the saying goes- ' All that glitters is not Gold', there are pitfalls and false positives in PSMAPET CT. In this education exhibit we shall review the basic concepts and uptake mechanisms of PSMA tracer and its physiologicalbio distribution. We shall present through pictoral review the various benign and malignant pathologies other than prostate whichshows PSMA avidity. Also the key pearls to differentiate, thus avoiding confounding factors and over calling .


1. Basic concepts regarding PSMA PET CT and the uptake mechanisms. 2. The normal Physiological uptake on PSMA scan. 3.Pictoral review of benign pathologies with uptake on PSMA. 4. Pictoral review of malignant pathologies other than prostate showingPSMA Avidity. 5. Clinical pearls to help avoiding confusion on PSMA Scans.


MI102-ED-X

3D Stereotactic Surface Projection of 18F-FDG Brain PET Improves Diagnosis of Neurological Disorders


ParticipantsIsrael Vicente Toledo Coronado, MD , Mexico City, Mexico (Presenter) Nothing to DiscloseRodrigo Hernandez Ramirez, Leon, Mexico (Abstract Co-Author) Nothing to DiscloseRicardo Martinez Martinez, MD, Mexico City, Mexico (Abstract Co-Author) Nothing to DiscloseDulce A. Sanchez Nava, MD, Mexico City, Mexico (Abstract Co-Author) Nothing to Disclose


[email protected]

TEACHING POINTS

1. To understand the 3D stereotactic projection as one of the PET analysis methods to quantify functional information related toneurodegenerative disease. 2. To describe the mechanism of 18F-FDG uptake in normal and abnormal neural tissue.3. To recognizethe characteristic patterns of brain metabolism in multiple neurological disorders based on case examples with multimodality imagingand clinical correlation.


1. Introduction2. Imaging techniques - FDG Brain acquisition 2.1 Mechanism of 18F-FDG uptake in normal and abnormal neuraltissue3. 3D sterotactic surface projection 3.1 Intensity normalisation 3.2 Anatomical standardisation4. Case examples inneurological disorders 4.1 Alzheimer´s disease 4.2 Frontotemporal dementia 4.3 Lewy body dementia 4.4 Encephalitis 4.4 Parkinsonplus syndrome 4.5 Epilepsy 4.6 Diferential diagnosis of dementia5. Summary and conclusions


MI103-ED-X

PET/CT in Multiple Myeloma: An Up-to-Date for Radiologists in Training



ParticipantsMaria J. Gutierrez, Buenos Aires, Argentina (Presenter) Nothing to DisclosePamela I. Causa Andrieu, MD, La Plata, Argentina (Abstract Co-Author) Nothing to DiscloseDaniel G. Perez, MD, Buenos Aires City, Argentina (Abstract Co-Author) Nothing to DisclosePablo E. Biedak, MD, Buenos Aires, Argentina (Abstract Co-Author) Nothing to DiscloseCristian Seehaus, Ciudad Autonoma de Buenos Aires, Argentina (Abstract Co-Author) Nothing to DiscloseAlberto C. Seehaus, MD, CABA, Argentina (Abstract Co-Author) Nothing to Disclose


[email protected]

TEACHING POINTS

Main applications of PET/CT are monitoring treatment and its predictive capacity. It's use is recommended in bone solitaryplasmocytoma, symptomatic or latent MM, or relapse.


PURPOSE: To exemplify with cases the PET/CT value in the handling of patients with multiple myeloma (MM). METHODOLOGY:Descriptive, observational, and retrospective study. 50 patients with diagnosis of MM followed with PET/CT between 01/30/2010and 12/31/2017. DISCUSSION: Whole-body X-Ray: Lytic lesions with no reactive sclerosis. More than 30% loss of cancellous boneneeded to detect lesions and difficult evaluation of pelvis and spine. WBLDCT Better evaluation of pelvis and spine. Full body MRI.Better sensitivity in axial skeleton bones. Evaluates radicular or medulla compression and latent MM. Diagnoses solitaryplasmocytoma. PET/CT: Osseous affection: 80% S & 100 % E in early stages. Evaluates response to treatment: discriminatesmetabolically active/non-active. Identifies minimal negative residual disease. Negative PET/CT after ABMT is good outcome earlypredictor. Positive PET/CT 3-6 months after complete response predicts bad outcome. Extramedullary disease and more than 3focal lesions after transplant imply a bad prognosis. Limitations: Lack of standardization in reports. High cost. Lack of availability.Lack of cost-effectiveness analysis studies.


MI104-ED-X

Synthetic MRI: Is that for You? Is that for Everyone?



ParticipantsCinthia G. Chaves, MD, Rio de Janeiro, Brazil (Presenter) Nothing to DiscloseFernanda C. Lopes, MD, Rio de Janeiro, Brazil (Abstract Co-Author) Nothing to DiscloseLuiz Celso Hygino, MD, Rio de Janeiro, Brazil (Abstract Co-Author) Nothing to DiscloseMarcio Bernardes, Rio de Janeiro, Brazil (Abstract Co-Author) Nothing to Disclose


[email protected]

TEACHING POINTS

? to point out different synthetic MRI software's pros and cons ? to review synthetic MRI applications ? to explore the possibilitiesfor quantitative mapping


? Synthetic MRI applications ? Synthetic MRI software's pros and cons ? Future prospects ? Summary


MI105-ED-X

Somatostatin Receptor-based Molecular Imaging in Diagnosis of Recurrent Meningioma



ParticipantsMing Yang, MD, Scottsdale, AZ (Presenter) Nothing to DiscloseAlyx B. Porter, MD, Scottsdale, AZ (Abstract Co-Author) Nothing to DiscloseSujay A. Vora, MD, Scottsdale, AZ (Abstract Co-Author) Nothing to DiscloseGeoffrey B. Johnson, MD,PhD, Rochester, MN (Abstract Co-Author) Research Grant, General Electric Company Research Grant, PfizerIncMacIej M. Mrugala, MD,PhD, Scottsdale, AZ (Abstract Co-Author) Nothing to DiscloseJonathan B. Ashman, MD,PhD, Scottsdale, AZ (Abstract Co-Author) Nothing to DiscloseMatthew L. King, RT, Scottsdale, AZ (Abstract Co-Author) Nothing to DiscloseJeffrey S. Ross, MD, Paradise Valley, AZ (Abstract Co-Author) Nothing to DiscloseBa D. Nguyen, MD, Scottsdale, AZ (Abstract Co-Author) Nothing to DiscloseMichael C. Roarke, MD, Scottsdale, AZ (Abstract Co-Author) Nothing to DiscloseDerek R. Johnson, MD, Rochester, MN (Abstract Co-Author) Nothing to Disclose


[email protected]

TEACHING POINTS

Meningioma is the most common brain tumor. Contrast-enhanced brain MRI is the gold standard in diagnosis. The mainstay oftherapy is surgical resection and/or radiosurgery. Tumor recurrence is not uncommon after initial treatment, which poses bothdiagnostic and treatment challenges as MRI is limited in depicting the recurrence in the presence of surgical and radiation scar.Meningioma usually has overexpression of somatostatin receptor (SSTR), especially subtype 2. The SSTR-based molecular imagingmodalities, including 111Indium(In)-Octreotide scintigraphy (OctreoScan) SPECT/CT and novel 68Ga-DOTATATE PET/CT, have beenused in delineation of meningioma given excellent tumor-to-background ratio. In this exhibit, we will 1. Review the basics of SSTR-based molecular imaging 2. Review the diagnostic performance of 111In-OctreoScan SPECT/CT in imaging meningioma 3. Introduce68Ga-DOTATATE PET/CT protocol/workflow in detection of recurrent meningioma 4. Demonstrate the added value of 68Ga-DOTATATE PET/CT in diagnosis of recurrent meningioma and its impact on clinical management.


1. WHO grading of meningioma 2. 111In-Octreoscan SPECT/CT in diagnosis of recurrent meningioma 3. 68Ga-DOTATATE PET/CTprotocol/workflow 4. Case illustration of 68Ga-DOTATATE PET/CT in recurrent meningioma 5. Common pitfalls of 68Ga-DOTATATEPET/CT imaging


MI106-ED-X

Beyond the Basics: 68Ga-DOTA-TATE PET/CT Pearls and Pitfalls


ParticipantsFaraz Farhadi, Bethesda, VA (Presenter) Nothing to DiscloseMoozhan Nikpanah, Bethesda, MD (Abstract Co-Author) Nothing to DiscloseBabak Saboury, MD, MPH, Baltimore, MD (Abstract Co-Author) Nothing to DiscloseElizabeth C. Jones, MD, Bethesda, MD (Abstract Co-Author) Nothing to DiscloseCorina Millo, MD, Bethesda, MD (Abstract Co-Author) Nothing to Disclose


[email protected]

TEACHING POINTS

Introducing the principles of somatostatin receptor (SSTR) expression and biology Utility of 68Ga-DOTA-TATE as an imagingtechnique in detection and characterization of neuroendocrine tumor (NETs) and other disorders with high somatostatin receptorexpression. Common pitfalls: •Not all the tracer avid lesions are NETs (mimickers). •How to avoid missing a lesion in an organ withnormal background uptake


SSTR expression and regulation. Dynamic interaction of Somatostatin Analogs (SSA) with SSTR. Basics of 68Ga-SSA PET/CTimaging and SUV measurement, including the effect of competitive inhibition in patients undergoing somatostatin analog therapy.Beyond the basics: 68Ga-SSA uptake in non-NETs: Meningioma Hemangioblastoma Breast Cancer Tumor Induced Osteolysis (TIO)Sarcoidosis Bone tumors Others How to avoid missing a tracer avid lesion when there is normal background uptake in the organ: apictorial review Intense, irregular update in sella Focal uptake in pancreas body Focal uptake in gastrointestinal tract Uptake inbone marrow


MI107-ED-X

Nuclear Medicine and Molecular Imaging in the Era of Theranostics


AwardsCertificate of Merit

ParticipantsKaitlyn Ellis, Lexington, KY (Presenter) Nothing to DiscloseHarit Kapoor, MD, Lexington, KY (Abstract Co-Author) Nothing to DiscloseAhmed H. Ragab, MBBCh, Alexandria , Egypt (Abstract Co-Author) Nothing to DiscloseM. Elizabeth Oates, MD, Lexington, KY (Abstract Co-Author) Nothing to DiscloseRiham H. El Khouli, MD,PhD, Nicholasville, KY (Abstract Co-Author) Nothing to Disclose

TEACHING POINTS

1. To understand the genesis, history and definition of Theranostics. 2. To identify examples of Theranostics in clinical practice. 3.To appraise the value of NM&MI in the era of Theranostics.


Theranostics is an emerging concept that describes an innovative approach to patient-centered cancer care, Precision Medicine.The term results from merging two words, therapy and diagnostics. Although the fundamental principles have been adopted byNM&MI for more than 75 years, the new sophisticated term is attracting much attention in the medical community. Understandingthe concept and application of Theranostics becomes essential for radiologists in general and nuclear radiologists in particular. Theeducational exhibit will follow this outline: 1. Describe the genesis, history and definition of Theranostics. 2. Highlight the originalapplication of Theranostics in clinical practice, namely, 131I radioiodine for diagnosis and treatment of hyperthyroidism in 1941. 3.Take the audience on a journey from 131I radioiodine to the most recent FDA-approved combination: diagnostic 68Ga-Dotatate/therapeutic 177Lu-dotatate. 4. Glimpse into the future through the research pipeline; one example is Prostate SpecificMembrane Antigen (PSMA) radiopharmaceuticals for prostate cancer.


MI108-ED-X

Reporter Gene Imaging and Its Potential Role in Drug Development


ParticipantsFaiq Shaikh, MD, Philadelphia, PA (Presenter) Researcher, Image Analysis Group; Research Consultant, Cellsight Technologies, LLCEwelina Kurtys, London, United Kingdom (Abstract Co-Author) Image Analysis GroupOlga A. Kubassova, PhD,MSc, Leeds, United Kingdom (Abstract Co-Author) Founder, Image Analysis Ltd CEO, Image Analysis LtdDiana Roettger, PhD, London, United Kingdom (Abstract Co-Author) Employee, Image Analysis LtdThomas Haywood, Stanford, CA (Abstract Co-Author) Nothing to Disclose


[email protected]

TEACHING POINTS

- Reporter gene imaging (RGI) involves imaging of encoding proteins that can be rapidly and sensitively assayed as surrogatemarkers when fused with regulatory regions of the gene of interest. - Modalities involved in RGI include MRI, PET, SPECT,Ultrasound, Bioluminescence, Fluoroscence, etc. - RGI imaging probes can be direct, indirect or activable; range from enzymes,protein receptors and cell membrane transporters. - RGI qualitatively and quantitatively assesses cell targeting, transfection,protein expression, intracellular processes, etc. - It can be used in drug development for pharmacodynamic and pharmacokineticassessment of cellular, gene, oncolytic viral and immunotherapeutic approaches.


- Introduction; - What is Reporter Gene Imaging?; - - What are Reporter genes; - - Molecular imaging probes; - - Direct andIndirect imaging; - - PET/SPECT; - - MRI; - - Optical imaging; - - - Near-infrared Imaging; - - - Bioluminescence imaging; - - -Fluorescence imaging; Novel therapeutics in development; - Immunotherapy; - Cell therapy; - Gene therapy; - Oncolytic viraltherapy; Role of RGI in Drug development; - Cell tracking; - Target molecule detection; - Oncolysis monitoring &pharmacodynamics; - Biodistribution and pharmacokinetics; - Quantifying therapeutic gene expression; - Evaluation of immunereactivity.


MI109-ED-X

Imaging-Guided Precision Medicine in Cancer Patients Treated with Immune Checkpoint Blockers


ParticipantsLaurent Dercle, MD, New York, NY (Presenter) Nothing to DiscloseSamy Ammari, Villejuif, France (Abstract Co-Author) Nothing to DiscloseAhmed Mekki, Villejuif , France (Abstract Co-Author) Nothing to DiscloseRomain-David Seban, Villejuif, France (Abstract Co-Author) Nothing to DiscloseRandy Yeh, MD, New York, NY (Abstract Co-Author) Nothing to DiscloseMathieu Sinigaglia, Paris , France (Abstract Co-Author) Nothing to DiscloseBinsheng Zhao, DSc, New York, NY (Abstract Co-Author) Royalties, Varian Medical Systems, Inc; License agreement, Keosys SAS;License agreement, Hinacom Software and Technology, Ltd; Fatima-Zohra Mokrane, MD, Toulouse Cedex 9, France (Abstract Co-Author) Nothing to DiscloseLawrence H. Schwartz, MD, New York, NY (Abstract Co-Author) Nothing to Disclose


[email protected]

TEACHING POINTS

1. To explain why immune checkpoint inhibitors are standard of care in many cancer types. 2. To review key elements that areexpected to improve the monitoring of immunotherapeutic efficacy. 3. To discuss new patterns of response and progression, as wellas immune related adverse events. 4. To explain the utility of imaging modalities in solid tumors, brain tumors and lymphomas.


I. PHYSIOPATHOLOGY: 1. The paradigm shift of immune oncology. 2. Current indications. II. NEW PATTERNS OF RESPONSE: 1.Hyperprogression, 2. Delayed efficacy, 3. Pseudoprogression and Indeterminate response, 4. Abscopal effect, 5. Mixed ResponsesIII. TOXICITY / IMMUNE RELATED ADVERSE EVENTS: 1. Frequency, 2. Sites, 3. Management IV. SPECIFIC RESPONSE EVALUATIONCRITERIA: 1. Solid tumors (irRECIST, irRC), 2. Brain tumors (iRANO), 3. Lymphoma (LYRIC). 4. Monitoring systemic vs. localinjections. V. IMAGING METABOLOMICS: 1. Cellular density, 2. Glucose metabolism, 3. Amino acid metabolism, 4. Membraneproliferation, 5. Growth hormones. VI. IMAGING ANGIOGENESIS, HYPOXIA: 1. Association with drug delivery, 2. Surrogate ofhypoxia, 3. Surrogate of vascularity. VII. IMAGING IMMUNE ENVIRONMENT: 1. Radiolabeled ICM, 2. Detecting CD8 and immuneenvironment. 3. TSPO. VIII. ARTIFICIAL INTELLIGENCE AND BIG DATA IX. PERSPECTIVES


ED015-SU

Molecular Imaging Sunday Case of the Day

Sunday, Dec. 1 7:00AM - 11:59PM Room: Case of Day, Learning Center

AMA PRA Category 1 Credit ™: .50

ParticipantsValeria Moncayo, MD, Atlanta, GA (Presenter) Nothing to DiscloseAkash Sharma, MD, Ponte Vedra Beach, FL (Abstract Co-Author) Nothing to DiscloseManoj K. Jain, MD, Jacksonville, FL (Abstract Co-Author) Nothing to DiscloseEphraim E. Parent, MD,PhD, Ponta Vedra Beach, FL (Abstract Co-Author) Research support, Blue Earth Diagnostics Ltd Researchsupport, Advanced Accelerator Applications SAOladunni O. Akin-Akintayo, MD,MPH, Atlanta, GA (Abstract Co-Author) Nothing to DiscloseYoram S. Baum, MD, Atlanta, GA (Abstract Co-Author) Nothing to DiscloseBruce J. Barron, MD, Atlanta, GA (Abstract Co-Author) Stockholder, Immunomedics, IncDhruv Patel, MD, Atlanta, GA (Abstract Co-Author) Nothing to DiscloseGabriela Spilberg, MD, Boston, MA (Abstract Co-Author) Nothing to DiscloseMarcelo F. Di Carli, MD, Boston, MA (Abstract Co-Author) Research Grant, Spectrum Dynamics Medical, Inc; Research Grant, GileadSciences, Inc; Research Consultant, General Electric Company; Research Consultant, sanofi-aventis Group; ; Vasvi Singh, MD, Boston, MA (Abstract Co-Author) Nothing to Disclose

TEACHING POINTS

1) Demonstrate the value of FDG PET-CT in evaluating infection. 2) Discuss the limitation of PET-CT for infection evaluation ascompared to other tracers. 3) Briefly review the role of other common radiotracer, e.g. In-111 WBC for this indication.


SSA13-01 Molecular Imaging Keynote Speaker: Artificial Intelligence in Neuroimaging

Sunday, Dec. 1 10:45AM - 11:05AM Room: S503AB

SSA13-03 Clinical-Radiological Features of Methotrexate Induced Sub-Acute Leukoencephalopathy in Patientswith Acute Lymphoblastic Leukemia: "Panda Eye Sign" on DW-MR Imaging


SSA13

Science Session with Keynote: Molecular Imaging (Neuroimaging)

Sunday, Dec. 1 10:45AM - 12:15PM Room: S503AB

MR MI NR

AMA PRA Category 1 Credits ™: 1.50ARRT Category A+ Credit: 1.75


ParticipantsPeter Herscovitch, MD, Bethesda, MD (Moderator) Nothing to DiscloseKarina Mosci, MD, Brasilia, Brazil (Moderator) Nothing to Disclose

Sub-Events

ParticipantsSatoshi Minoshima, MD, PhD, Salt Lake City, UT (Presenter) Consultant, Hamamatsu Photonics KK; Research Grant, Hitachi, Ltd;Research Grant, Nihon Medi-Physics Co, Ltd;

ParticipantsAbhishek Mahajan, MBBS,MD, Mumbai, India (Presenter) Nothing to DiscloseHasmukh Jain, Mumbai, India (Abstract Co-Author) Nothing to DiscloseTanvi Vaidya, Mumbai, India (Abstract Co-Author) Nothing to DiscloseSanthosh K. G V, MD , Bangalore, India (Abstract Co-Author) Nothing to DiscloseAnurag Gupta, MD, Mumbai, India (Abstract Co-Author) Nothing to DiscloseManju Sengar, MD, Mumbai, India (Abstract Co-Author) Nothing to Disclose


[email protected]

PURPOSE

Subacute leukoencephalopathy in ALL is a rare complication after high dose methotrexate (HDMTX) administration and recognizingthis self-remitting entity has important therapeutic implications. We did a retrospective study to evaluate the role of MR imaging indiagnosing this entity and asses the incremental value of Qualitative and Quantitative diffusion weighted MR (DW-MRI).

METHOD AND MATERIALS

A retrospective review of database was performed for adolescent and adult ALL (Aged>14 years) patients who were treated at ourcenter with the modified Berlin-Frankfurt-Münster (BFM)-90 protocol (BFM-90 protocol). 438 patients were screened from year2014-2015, of which 239 patients were eligible for the BFM-90 protocol. All patients were treated with high dose methotrexate(>1g/m2) and presented with new onset of neurological disturbances were identified. Eleven patients of ALL aged >14 years whodeveloped acute onset of neurological symptoms within two weeks (14 days) after administration of high dose methotrexate andunderwent CT and MR imaging with diffusion weighted MR imaging (with 48 hours of presentation) were analyzed. The mean mADCvalues (10-3 cm2/sec) were calculated on a voxel-by-voxel basis using ADW 4.4 software provided with the MR imaging unit.

RESULTS

Eleven patients were identified from a cohort of 239 patients (~5%). They presented with focal neurological deficits within ~14days after HDMTX that resolved completely with conservative measures. The CT scans were normal in all these patients. Aconsistent finding seen in all these cases was the occurrence of restricted diffusion in the region of the centrum semiovale on DW-MRI. On diffusion maps, symmetrical areas of hyperintensity resembled 'Panda eyes' and mADC cut-off of our series was 0.000453 x10-3 +/- 0.000120 cm2/sec.

CONCLUSION

CT brain and Conventional MR imaging have no significant role to play in diagnosing this entity however restricted in the centrumsemiovale is a consistent imaging finding and the "panda eye sign" as seen on DW imaging can be considered diagnostic formethotrexate induced subacute leukoencephalopathy and this sign can help in timely establishment of the diagnosis and appropriatemanagement.

CLINICAL RELEVANCE/APPLICATION

The literature is limited on incremental of colored diffusion maps and mean apparent diffusion co-efficient (mADC) values and theirrole in diagnosing MIN.

SSA13-04 Biotin-Conjugated Upconversion Nanoparticles for Metabolic MR Imaging of Invasive Margin ofGlioma


SSA13-05 Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Monitoring the Anti-angiogenesisEfficacy in a C6 Glioma Rat Model


ParticipantsHua Zhang, Shanghai, China (Presenter) Nothing to Disclose

PURPOSE

To prepare one stable biotinylated/polyethylene glycolylated upconversion nanoprobes (biotin/PEG-UCNPs) to study the expressionlevel of biotin receptor in GL261 glioma and its feasibility for detection invasive margin of glioma


Hydrophobic multifunctional upconversion nanoparticles (UCNPs) were synthesized by solvothermal method. TEM, XRD ,fluorolog-3modular fluorescence spectrometer and other instruments were used to analyze the surface features such as uniformity anddispersion of nanoprobes. Cell counting kit-8 (CCK-8) analyzed the effect of bion-UCNPs on the activity of RAW264.7 and BCECs.CLSM was used to observe the endocytosis efficiency of GL261 glioma cells for biotinylated and non-biotinylated nanoprobes, thenthe distribution of nanoprobes in glioma tissues compared with pathology. GE Discovery 3.0T MR analyzed the relaxation rate ofbiotinylated nanoprobes and the relative signal intensity (rSI) of biotinylated nanoprobes in gliomas at different time points. HEstaining of cortical, striatum, hippocampal and hematological parameters of normal C57BL/6 mice were evaluated the potentialtoxicity of biotinylated nanoprobes to living organisms.

RESULTS

Biotinylated nanoprobes with similar particle size (particle size of about 25 nm) possessed good dispersibility, low toxicity andsingle-band UCL spectrum centered at 660 nm. The relaxation rate reached 6.124 mM-1S-1. Under CLSM, the glioma cellssignificantly endocytosed biotinylated nanoprobes rather than the non-biotinylated nanoprobes. After biotin receptor presaturation,the glioma cell endocytosis was significantly reduced. T1 signal generated by the biotinylated nanoprobes in the glioma region couldstill be observed in 24 hours, and the tumor developing area was expanding. The body boundary of biotinylated nanoprobes wellcorresponded to the HE-stained glioma border, but the tumor cells were scattered around the boundary. No obvious adversereactions were observed in the cortical, striatum, hippocampal.

CONCLUSION

GL261 gliomas highly express biotin receptors. Biotinylated UCNPs are able to efficiently target glioma via biotin receptors, and showa significant contrast effect on the edge of glioma invasion.


(dealing with invasive margin of glioma) Biotin-UCNPs can explicitly demonstrate the glioma cells scattered around the boundary viabiotin receptor

ParticipantsWeishu Hou, Hefei, China (Presenter) Nothing to DiscloseXiaohu Li, MD, Hefei, China (Abstract Co-Author) Nothing to DiscloseHongli Pan, Hefei, China (Abstract Co-Author) Nothing to DiscloseMan Xu, Hefei, China (Abstract Co-Author) Nothing to DiscloseYinfeng Qian, Hefei, China (Abstract Co-Author) Nothing to DiscloseYongqiang Yu, MD, Hefei, China (Abstract Co-Author) Nothing to Disclose


[email protected]

PURPOSE

To observe the changes of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters in monitoring the earlyeffects of antiangiogenic therapy in a C6 glioma rat model.


Twenty-six rats were used to establish a C6 glioma model and were randomly divided into a treated group (n = 13) and a controlgroup (n = 13). Rats in the treated group were administered with bevacizumab (Bev) for 7 days, while rats in the control groupwere administered with vehicle at the same dose. Conventional MRI and DCE-MRI scans were obtained, respectively, on days 0, 1,3, 5, and 7 after treatment; tumor volume and MRI parameters were dynamically observed. Hematoxylin and eosin (HE) andimmunohistochemical (IHC) examination including MVD and proliferating cell nuclear antigen (PCNA) were performed on day 7. One-way ANOVA was used to compare intra-group differences in each group and t-test was used to compare inter-group differences ofMRI parameters between the two groups. Correlations between MRI quantitative parameters and IHC scores were analyzed.

RESULTS

The tumor volume and relative change of tumor volume in the treated group were significantly lower than that of control group onday 7 after treatment with Bev. Ktrans and Kep decreased in the treated group while they increased in the control group; Veincreased in the treated group while it decreased in the control group. A significant difference in MRI parameters between the twogroups was observed on days 5 and 7 after treatment. Ktrans and Kep showed positive correlations with MVD, while Ve showednegative correlation with PCNA.

CONCLUSION

DCE-MRI dynamically and accurately assessed the early effects of anti-angiogenic therapy against tumors and may be used as a

SSA13-06 The Correlation Analysis of MR Diffusion Tensor Imaging: MR Perfusion Weighted Imaging andFluorine-18-deoxyglucose Positron Emission Tomography in Patients with Malignant Brain Tumors


SSA13-07 Radiomic Classification of Tumors Based on Tumor-Associated Macrophage Burden


therapeutic strategy.


DCE-MRI can assessed effects of anti-angiogenic therapy of glioma.

ParticipantsXiang Liu, MD, Rochester, NY (Presenter) Nothing to DiscloseWei Tian, MD,PhD, Rochester, NY (Abstract Co-Author) Nothing to DiscloseHenry Z. Wang, MD, PhD, Pittsford, NY (Abstract Co-Author) Nothing to Disclose


Xiang_LIu@URMC>Rochester.edu

PURPOSE

MR diffusion tensor imaging (DTI), MR dynamic susceptibility contrast perfusion weighted imaging (DSC-PWI), and fluorine-18-deoxyglucose (FDG) positron emission tomography (PET) are major clinical advanced imaging techniques for malignant brain tumors.The purpose of this study is to evaluate the correlation between MR DTI and PWI parameters and FDG-PET changes in patientswith malignant brain tumors.


75 paired MR DTI, DSC-PWI and FDG-PET examinations in 62 patients with malignant brain tumors, including high grade gliomas,brain metastases and cerebral lymphomas, were enrolled in this study. The interval between MR (DTI and DSC-PWI) and FDG-PETexaminations ranged from 0 to 13 days in 66 paired MR DSC-PWI and FDG-PET examinations, another 6 paired stable post-surgicalscans were acquired within 28 days. The ADC, FA and rCBV maximal rCBV ratio without and with contrast leakage correction weremeasured using FDA-approved GE BrainStat and NordicICE programs. The tumor versus normal tissue count ratio (TNR) in the "hot"ROIs were calculated for comparison. The correlations between minimal ADC, maximal FA and maximal rCBV ratio of rCBV withoutand with contrast leakage correction and TNR were evaluated with Spearman Rank correlation analysis.

RESULTS

There was no significant correlation between ADC and FA and TNR derived from FDG-PET (p>0.05). The mean maximal rCBV ratio ofrCBV with contrast leakage correction (1.88±1.41) were higher than rCBV without contrast leakage correction (1.19 ± 0.77,p<0.05). The rCBV with contrast leakage correction has better correlation with FDG-PET-TNR than rCBV without contrast leakagecorrection, p<0.001. Figure 1.

CONCLUSION

The rCBV with contrast leakage correction shows better correlation with FDG-PET-TNR. Combination of MR DTI, MR-DSC-PWI andFDG-PET parameters could provide comprehensive information of tumor microstructure, hemodynamic and metabolic abnormality.


Combination of MR DTI, MR-DSC-PWI and FDG-PET parameters could provide comprehensive information of tumor microstructure,hemodynamic and metabolic abnormality.

ParticipantsZbigniew Starosolski, PhD, Houston, TX (Abstract Co-Author) Stockholder, Alzeca Biosciences, LLCAmy Courtney, Houston, TX (Abstract Co-Author) Nothing to DiscloseIgor Stupin, Houston, TX (Abstract Co-Author) Nothing to DiscloseLinjie Guo, Houston, TX (Abstract Co-Author) Nothing to DiscloseAnanth Annapragada, PhD, Houston, TX (Abstract Co-Author) Stockholder, Alzeca Biosciences, LLC; Stockholder, Sensulin, LLC;Stockholder, Abbott Laboratories; Stockholder, Johnson & Johnson; Research Grant, Alzeca Biosciences, LLCLeonid Metelitsa, MD,PhD, Houston, TX (Abstract Co-Author) Nothing to DiscloseKetan B. Ghaghada, PhD, Houston, TX (Presenter) Research Consultant, Alzeca Biosciences, LLC


[email protected]

PURPOSE

A high burden of tumor-associated macrophages (TAMs) has been correlated with an aggressive disease phenotype and poorprognosis in several cancer types. Non-invasive imaging techniques for stratifying tumors based on TAM burden could help intreatment planning and monitoring response to immune-directed therapies. In this pre-clinical study, we investigated a radiomicsapproach for the stratification of solid tumors based on TAM burden.


Studies were performed in transgenic mouse models of neuroblastoma (NB) with low and high TAM burden. The SV40-induced NBmouse model, which develops spontaneous adrenal tumors (NB-Tag), was used as a model of low TAM burden (n=5). Knock-out NB-Tag mouse models lacking Ja18 (Ja18-/-) (n=6) or CD1d (CD1d-/-) (n=4) were used as models of high TAM burden. The high TAMburden in knock-out models was confirmed by flow cytometry. Contrast-enhanced CT (CECT) imaging was performed four daysafter administration of a liposomal-iodine (Lip-I) nanoparticle contrast agent. Tumors were segmented in CT images andquantitative radiomic analysis was performed using an open-source software (PyRadiomics). A Wilcoxon statistical test was used for

SSA13-08 Long-Duration MRI Imaging of Single-Cell In-Vivo and In-Vitro via Magnetic Vortex Nanorings

Sunday, Dec. 1 11:55AM - 12:05PM Room: S503AB

SSA13-09 Quantification of Blood Spinal Cord Barrier Opening After Application of Magnetic Resonance GuidedFocused Ultrasound

Sunday, Dec. 1 12:05PM - 12:15PM Room: S503AB

selection of radiomic features.

RESULTS

Average tumor CT signal did not differ significantly between tumors in low and high TAM burden groups. However, radiomic analysisidentified 49 features that differentiated (p<0.05) low TAM tumors from high TAM CD1d-/- tumors, and 31 features thatdifferentiated (p<0.05) low TAM tumors from high TAM Ja18-/- tumors. Subsequently, tumors in two high TAM burden groups(CD1d-/- and Ja18-/-) were pooled together and compared against tumors in low TAM NB-Tag group to determine if radiomicanalysis differentiated tumors based on TAM burden but independent of knock out model. Analysis yielded 26 features thatseparated (p<0.05) low TAM tumors from high TAM tumors. Radiomic features based on first order statistics and gray level sizezone matrix represented the dominant set of features that enabled separation of tumors based on TAM burden, suggesting markedlydifferent tumor texture in CECT images in low and high TAM burden tumors.

CONCLUSION

Radiomic analysis identified texture-based features that stratified tumors based on macrophage burden.


Radiomics may enable surveillance of immune cell burden in solid tumors.

ParticipantsRan Sun, Chengdu, China (Presenter) Nothing to DiscloseLiu Hanrui, Chengdu , China (Abstract Co-Author) Nothing to DiscloseYingkun Guo, Chengdu, China (Abstract Co-Author) Nothing to DiscloseHaiming Fan, Xian, China (Abstract Co-Author) Nothing to Disclose


[email protected]

PURPOSE

To develop an ultra-high sensitive MRI contrast agent for long-term in vivo and in vitro single-cell tracking, which can escape earlylysosomes into cytoplasm, especially under the disturbance of alternating magnetic field.


Bone marrow mesenchymal stem cells (BMSCs) of SD rats were labeled with 50 µg/ml Fe ferrimagnetism vortex magnetic nanorings(FVIOs). In vitro MRI was performed on three groups with number of 1, 5 and 10 labeled BMSCS. For in vivo imaging, 10, 100 and1000 labeled BMSCs were injected into SD rats' brain via stereotaxis technology and scanned at 7T SWI (susceptibility weightedimaging). After 1h of co-culture of BMSCs and nanorings, alternating magnetic field (AMF) were added for minutes of continuousinterference. Another 23h co-culture was performed, then BMSCs were stained and lysosomal escape effect was detected underconfocal microscope. GFP-transfected BMSCs were co-cultured with FVIOs by the same method and transplanted into the striatumof SD rats according to the number of cells for long-term magnetic resonance detection.

RESULTS

From the in vitro 7T MRI images, the signals of single FVIOs labeled BMSCs could be clearly detected compared with contractgroups. And the in vivo results shows that at least 10 transplanted BMSCs in SD rats' brain could be detected by strong MRI signal.Confocal results also shows that AFM disturbance could successfully facilitate FVIOs to escape from lysosomes into cytoplasm in 10minutes at early period of co-culture of BMSCs and FVIOs . The same FVIOs labeled GFP-MSCs were transplanted into rats' brainand also could be detected for more than 8 weeks at 7T MRI. Immunofluorescence histochemical analysis showed that sometransplanted cells were still alive and corresponding to the signal position detected by MRI.

CONCLUSION

The FVIOs we reported had ultra-high MRI sensitivity to accurately track single cell both in vitro and in vivo, as well as succeed inescaping the lysosome under the interference of alternating magnetic field.


Ferrimagnetism vortex magnetic nanorings has a broad prospect of clinical application because of its low toxicity, low dose and highsensitivity. Its high safety and efficiency surpasses the contrast agents currently used in clinic. In addition, it provides a robusttracer technology support in the further treatment of stem cells and promote stem cell treatment to the clinic faster and better.

AwardsTrainee Research Prize - Medical Student

ParticipantsChloe G. Cross, BSC, Salt Lake City, UT (Presenter) Nothing to DiscloseAllison Payne, PhD, Salt Lake City, UT (Abstract Co-Author) Nothing to DiscloseGregory W. Hawryluk, Salt Lake City, UT (Abstract Co-Author) Nothing to DiscloseRiley Haag-Roeger, Salt Lake City, UT (Abstract Co-Author) Nothing to DiscloseRahul Cheeniyil, Salt Lake City, UT (Abstract Co-Author) Nothing to DiscloseHenrik Odeen, PhD, Salt Lake City, UT (Abstract Co-Author) Nothing to DiscloseSatoshi Minoshima, MD, PhD, Salt Lake City, UT (Abstract Co-Author) Consultant, Hamamatsu Photonics KK; Research Grant,Hitachi, Ltd; Research Grant, Nihon Medi-Physics Co, Ltd;

Donna J. Cross, PhD, Salt Lake City, UT (Abstract Co-Author) Nothing to DiscloseYoshimi Anzai, MD, Salt Lake City, UT (Abstract Co-Author) Nothing to Disclose


[email protected]

PURPOSE

To develop observer-independent MRI quantification of blood spinal cord barrier (BSCB) permeability after magnetic resonanceguided focused ultrasound (MRgFUS) in spinal cord injury (SCI).


Rats (n=21) underwent T8-T10 laminectomy and extradural compression of the spinal cord (23g weighted aneurysm-type clip, 1min). High-resolution T1w MR images (3T Siemens, 3D VIBE, FOV=162 mm162 mm×45 mm, res=0.4 mm×0.4mm×0.8 mm interpolatedto 0.2 mm×0.2 mm×0.4 mm, TR/TE=6.21/2.94 ms, FA=10°) were obtained pre-MRgFUS without contrast, pre-MRgFUS half-dosecontrast, and post-MRgFUS full-dose contrast (Gadoteridol, 0.25 mL/kg, 0.1 mL saline). Rats (n=11) were placed on a MRgFUSsystem (256-element phased-array transducer, f=940 kHz, focal depth=10cm, intensity FWHM=1.8×2.5×10.9 mm3), injectedOptison microbubbles (0.2 mL/kg, 0.1 mL saline) and received 3 doses in 4 locations, 2 mm apart (25 ms bursts, 1 Hz pulses for 3min, 1.0-2.1 MPa peak pressure). Shams (n=10) received equivalent procedures with no sonications. Spinal cords were segmentedmanually or semi-automatically using the Spinal Cord Toolbox. SCI rats post-MRgFUS average ROI intensity were normalized to pre-MRgFUS half-contrast. Non-injured rats (n=3) were administered Evans Blue post-MRgFUS and spinals cords were sectioned into 5mm x 7 samples. Absorbance was measured by spectrophotometry at 655 nm per mg tissue and correlated to post-MRgFUS ROIsnormalized to pre-MRgFUS.

RESULTS

Semi-automatic segmentation reduced time by 95% and showed no difference to the manual method (Pearson = 0.92, p=.00001,n=71 regions). Evans Blue absorbance correlated to image intensity in MRgFUS and control ROI (Pearson = 0.82, p=.02, n=6).Increase in signal intensity in MRgFUS ROI relative to control was seen in all SCI MRgFUS rats (10.65±12.4%, range: 0.96-43.9%,n=11). SCI sham MRgFUS revealed no change (0.63±0.52%, range: 0.15-1.63%, n=10). This result was significant between bothgroups (p=.003).

CONCLUSION

Semi-automatic segmentation of the rat spinal cord was successful. Evans Blue absorbance was correlated to image intensityvalues in non-injured rats. Quantitative methods are sensitive for detection of BSCB opening induced by MRgFUS in the SCI animalmodel.


Most potential therapeutics for SCI require invasive (surgery) or semi-invasive (intrathecal) delivery. The use of MRgFUS to openthe BSCB and deliver therapeutics will facilitate recovery from SCI.


MI200-SD-SUA1

MRI Relaxometry for Tracking Nanoparticle Mediated Ablation Therapy of Colorectal Cancer LiverMetastasis

Station #1

MI215-SD-SUA3

Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Monitoring The Anti-AngiogenesisEfficacy in a C6 Glioma Rat Model Dynamic Contrast-Enhanced Magnetic Resonance Imaging forMonitoring the Anti-Angiogenesis Efficacy in a C6 Glioma Rat Model

Station #3

MIS-SUA

Molecular Imaging Sunday Poster Discussion

Sunday, Dec. 1 12:30PM - 1:00PM Room: MI Community, Learning Center

MK MR NM NR US MI OI BQ


ParticipantsGabriel C. Fine, MD, Salt Lake City, UT (Moderator) Nothing to Disclose

Sub-Events

ParticipantsEl-Sayed H. Ibrahim, PhD, Milwaukee, WI (Presenter) Nothing to DiscloseAbdul K. Parchur, PhD, Milwaukee, WI (Abstract Co-Author) Nothing to DiscloseGayatri Sharma, PhD, Milwaukee , WI (Abstract Co-Author) Nothing to DiscloseJaidip Jagtap, PhD, Milwaukee, WI (Abstract Co-Author) Nothing to DiscloseChristopher Hansen, Milwaukee, WI (Abstract Co-Author) Nothing to DiscloseVenkateswara R. Gogineni, PhD, Milwaukee, WI (Abstract Co-Author) Research support, Instylla; Research support, Guerbet SA;Research support, InSightec LtdPeter S. Laviolette, Milwaukee, WI (Abstract Co-Author) Nothing to DiscloseMichael H. Flister, Milwaukee, WI (Abstract Co-Author) Nothing to DiscloseSarah B. White, MD, Milwaukee, WI (Abstract Co-Author) Research support, Guerbet SA; Research support, Siemens AG; Researchsupport, Instylla; Research support, InSightec Ltd; Consultant, Guerbet SA; Consultant, BTG International Ltd; Consultant, CookGroup Incorporated; Consultant, Strategies MDAmit Joshi, PhD, Houston, TX (Abstract Co-Author) Nothing to Disclose

PURPOSE

Surgical intervention is only possible in less than one third of colorectal liver metastases cases. Chemotherapy and hyperthermiaablation are the only other clinically available treatment options. In this respect, detecting accurate tumor location during thetherapeutic procedures is essential to effective treatment. In this study, we explore the value of MRI relaxometry for identifying thetumor response to theranostic nanoparticles (TNPs) mediated photothermal therapy (PTT) and distinguishing it from normalsurrounding tissues.


Au nanorods resonant at 830nm were synthesized, and encapsulated with Gd2O3:Yb/Er shell and PEGylated, resulting in formationof sub-100 nm TNPs. Three WAG/RijCmcr rats implanted with colorectal cancer liver metastasis (CLRM) tumors were scanned on9.4T MRI scanner. TNPs (0.5 mL, 1013 NP/mL) were locally injected into the liver via hepatic portal vein. The rats were imaged todetermine MRI R2* relaxometry immediately after TNPs injection, followed by 3-minute laser ablation (~700 mW/cm2), and at 10days post procedure. R2* relaxometry was assessed using a gradient-echo T2* mapping sequence to acquire axial and coronalstacks of 6-12 images covering the liver. Nine echoes were acquired with echo times ranging from 4ms to 48ms in 5.5msincrements. R2* was measured for each pixel as 1000/T2*, and the results were used to generate R2* maps.

RESULTS

The TNPs' R1 =1.1 × 108 mM-1 s-1 and R2 =4.8 × 108 mM-1 s-1. The CLRM tumor R2* =25.2±0.6 s-1 in post-PTT rats, which is~5 times higher than normal liver R2* relaxivity (5.9±0.6 s-1). The tumor R2* relaxivity decreased to 15.3±0.9 s-1 at 10-days posttherapy, which is ~3 times higher than normal value in the liver (5.9±0.6 s-1). The results showed significant difference betweenR2* values in tumor and normal tissues at the two imaging timepoints.

CONCLUSION

In conclusion, inclusion of MRI contrast in gold nanoparticles with plasmon resonance in near-infrared optical region can play asignificant role in precise image-guided PTT by accurately tracking the tumor boundaries, which enables high-efficiency PTT bydelivering a sufficient amount of light to the tumor.


MRI contrast can be used for targeting colorectal cancer liver metastasis tumors, which enables delivering sufficient amount of lightduring photothermal tumor ablation and tracking therapy response.

ParticipantsWeishu Hou, Hefei, China (Presenter) Nothing to DiscloseXiaohu Li, MD, Hefei, China (Abstract Co-Author) Nothing to Disclose

MI110-ED-SUA4

Molecular Imaging and Theranostics in Pheochromocytoma and Paraganglioma

Station #4

Hongli Pan, Hefei, China (Abstract Co-Author) Nothing to DiscloseMan Xu, Hefei, China (Abstract Co-Author) Nothing to DiscloseYinfeng Qian, Hefei, China (Abstract Co-Author) Nothing to DiscloseYongqiang Yu, MD, Hefei, China (Abstract Co-Author) Nothing to Disclose


[email protected]

PURPOSE

To observe the changes of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters in monitoring the earlyeffects of antiangiogenic therapy in a C6 glioma rat model.


Twenty-six rats were used to establish a C6 glioma model and were randomly divided into a treated group (n = 13) and a controlgroup (n = 13). Rats in the treated group were administered with bevacizumab (Bev) for 7 days, while rats in the control groupwere administered with vehicle at the same dose. Conventional MRI and DCE-MRI scans were obtained, respectively, on days 0, 1,3, 5, and 7 after treatment; tumor volume and MRI parameters were dynamically observed. Hematoxylin and eosin (HE) andimmunohistochemical (IHC) examination including MVD and proliferating cell nuclear antigen (PCNA) were performed on day 7. One-way ANOVA was used to compare intra-group differences in each group and t-test was used to compare inter-group differences ofMRI parameters between the two groups. Correlations between MRI quantitative parameters and IHC scores were analyzed.

RESULTS

The tumor volume and relative change of tumor volume in the treated group were significantly lower than that of control group onday 7 after treatment with Bev. Ktrans and Kep decreased in the treated group while they increased in the control group; Veincreased in the treated group while it decreased in the control group. A significant difference in MRI parameters between the twogroups was observed on days 5 and 7 after treatment. Ktrans and Kep showed positive correlations with MVD, while Ve showednegative correlation with PCNA.

CONCLUSION

DCE-MRI dynamically and accurately assessed the early effects of anti-angiogenic therapy against tumors and may be used as atherapeutic strategy.


DCE-MRI can assessed effects of anti-angiogenic therapy of glioma.

ParticipantsSara Sheikhbahaei, MD, Baltimore, MD (Presenter) Nothing to DiscloseSteven P. Rowe, MD, PhD , Baldwin, MD (Abstract Co-Author) Research funded, Progenics Pharmaceuticals, IncLilja B. Solnes, MD, Baltimore, MD (Abstract Co-Author) Advisory Board, Progenics Pharmaceuticals, Inc


[email protected]

TEACHING POINTS

This education exhibit provides a case-based review of the role of molecular imaging in the diagnosis, staging, and follow-up ofpatients with pheochromocytoma and paragangliomas (PPGLs). This includes reviewing the mechanism of different functionalimaging modalities, and proposed algorithm for imaging of PPGLs. We discuss the application, efficacy and adverse reactions oftargeted radiotherapy in PPGLs.


1. Background- Classification and clinical spectrum of Pheochromocytoma and Paragangliomas (PPGLs) 2. Metabolic imagingphenotypes in PPGLs including catecholamine metabolism, somatostatin receptors, and glucose uptake imaging 3. Appropriate usecriteria and clinical algorithm for molecular imaging of PPGLs 4. Physiologic bio-distribution, and pitfalls in interpretation of 123I-MIBGand 68Ga-DOTA SSA PET imaging 5. Application, efficacy and adverse reaction of targeted radiotherapies in PPGLs including theFDA approved 131I- iobenguane (AZEDRA) therapy and potentially 177Lu-DOTATATE (Lutathera) 6. Future directions


MI202-SD-SUB1

Ultrasound-Mediated Targeted Delivery of Dexamethasone Using Phase-Change Nanodroplets for theTreatment of Rheumatoid Arthritis

Station #1

MI203-SD-SUB2

Relationship between Parameters of Intravoxel Incoherent Motion Diffusion-Weighted Imaging withKi-67 Level in Cervical Cancer

Station #2

MIS-SUB

Molecular Imaging Sunday Poster Discussion

Sunday, Dec. 1 1:00PM - 1:30PM Room: MI Community, Learning Center

MI



ParticipantsGabriel C. Fine, MD, Salt Lake City, UT (Moderator) Nothing to Disclose

Sub-Events

ParticipantsBihui Zhu, Chengdu, China (Presenter) Nothing to DiscloseLiyun Wang, MD,PhD, Chengdu, China (Abstract Co-Author) Nothing to DiscloseLi Qiu, Chengdu, China (Abstract Co-Author) Nothing to Disclose


[email protected]

PURPOSE

To develop an ultrasound-responsive nanosystem for the targeted treatment of rheumatoid arthritis (RA).


The Dex-NDs-FA consisting of a lipid shell, perfluoro-n-pentane core and Dex were synthesized using a thin-film hydration andsonication method. The size and zeta potential were measured by dynamic light scattering and the morphology was observed usingthe TEM. Dialysis diffusion method was used to investigate the efficiency of Dex release and the thermal evaporation of Dex-NDs-FA was visualized using CEUS mode. For in vitro cell testing, the cytotoxicity and cellular uptake of Dex-NDs-FA conducted on RAW264.7 cells were assessed by MTT tests, flow cytometry and confocal laser scanning microscopy, respectively. Moreover, the invivo anti-inflammatory efficiency was observed after intravenous injection of Dex-NDs-FA into collagen-induced arthritis (CIA) rats.The statistical significance among the groups was performed with one-way ANOVA.

RESULTS

The Dex-NDs-FA were spherical in shape with an average size of 311.6 ± 3.8 nm and zeta-potential of -3.11 ± 0.15 mV. The 1 MHzultrasound (US) could enhance the drug release and the total cumulative release rates of US-treated group was 85.6 ± 4.3%. Inaddition, the contrast signals measured by the diagnostic US proved that the occurrence of vaporization was depended ontemperature. The US-mediated high-concentration of Dex-NDs-FA showed the highest in vitro cytotoxicity on activated RAW264.7cells (p<0.05), and the cellular uptake tests demonstrated that nanodroplets modified with folate could enhance the uptake ofactivated cells. Moreover, the US-mediated Dex-NDs-FA exhibited excellent inhibition of synovitis and joint destruction in CIA rats.

CONCLUSION

The Dex-NDs-FA were successfully synthesized with around 300 nm in diameter, which showed good feasibility for passive targetingdelivery into inflammatory tissue through EPR effect. Moreover, the Dex-NDs-FA could be effectively internalized by cells and showcytotoxicity on macrophages in high-concentration drug with US. Furthermore, the significant suppression of inflammation wereachieved in vivo through the Dex-NDs-FA with US, acting as an efficient targeted agent for RA therapy.


Our work offers a new strategy to the treatment of RA and US-mediated phase-change nanodroplets would have a great potentialfor the application in the areas of theranostic agent and medical treatment.

ParticipantsCuiping Li, Hefei, China (Presenter) Nothing to DiscloseMingxue Zheng, Hefei, China (Abstract Co-Author) Nothing to DiscloseDong Jiangning, Hefei, China (Abstract Co-Author) Nothing to Disclose

PURPOSE

Based on diffusion weighted imaging(DWI) and intravoxel incoherent motion diffusion weighted imaging(IVIM-DWI),to explorewhether there is a statistical difference between the Ki-67 level and apparent diffusion coefficient(ADC) value,IVIM-DWI multi-parameter value (D value, D* value and f value) in cervical cancer.

MI216-SD-SUB3

Longitudinal Analysis of Molecular Imaging Identifies Short Term Recurrence in Glioblastoma Treatedwith Bevacizumab

Station #3

MI111-ED-SUB4

Peptide Receptor Radionuclide Therapy (PRRT): 2019 Update

Station #4


A retrospective study was performed on totally 67 patients with cervical cancer confirmed by surgery. All patients underwentmultiple b-values(b=0,10,20,50,100,200,400,800,1000,2000 s/mm2)DWI before any anticancer treatment. The patients weredivided into low expression group (Ki-67 <50%) and high expression group (Ki-67>=50%) according to the expression level of Ki-67.Relationship between the ADC value,the quantitative parameters from IVIM and the expression level of Ki-67 was assessed usingindependent sample t-test.

RESULTS

In high Ki-67 group, the mean D, D* and f value had significantly differences compared with those of the low Ki-67group[(0.60±0.13)×10-3mm2/s vs (0.51±0.14)×10-3mm2/s,p=0.037,AUC=0.684; (19.48±14.18)×10-3mm2/s vs (8.85±6.53)×10-3mm2/s,p<0.001, AUC=0.760; (0.28±0.14)×10-3mm2/s vs (0.41±0.15)×10-3mm2/s,p=0.011, AUC=0.232].While the mean ADCvalue had no statistical significance between two groups((0.77±0.10)×10-3mm2/s vs (0.74±0.08)×10-3mm2/s,p=0.413).

CONCLUSION

The pre-treatment quantitative parameters D,D* values from IVIM model are of great value in predicting the Ki-67 level of thecervical cancer. Suggesting that the Ki-67 level can be predicted by non-invasive imaging examination, and thus clinical guidancecan be provided.


Ki-67 level can be predicted by non-invasive imaging examination and clinical guidance can be provided.

ParticipantsLeehi Joo, MD, Daegu, Korea, Republic Of (Presenter) Nothing to DiscloseJi Eun Park, Seoul, Korea, Republic Of (Abstract Co-Author) Nothing to DiscloseHo Sung Kim, MD, Seoul, Korea, Republic Of (Abstract Co-Author) Nothing to DiscloseHyunjin Kim, MD, Seongnam-si, Korea, Republic Of (Abstract Co-Author) Nothing to DiscloseDonghyun Kim, MD, Busan, Korea, Republic Of (Abstract Co-Author) Nothing to DiscloseHye Young Heo, Baltimore , MD (Abstract Co-Author) Nothing to Disclose


[email protected]

PURPOSE

To test the capability to aid prediction of clinical outcome, including 6-month and 12-month progression, and overall survival (OS)in recurrent glioblastoma treated with bevacizumab using amide proton transfer-weighted (APTw) imaging and diffusion-weighedimaging.


Multimodal MRI of 40 patients treated for recurrent glioblastoma were retrospectively selected at 4 time points: baseline, initialfollow up after bevacizumab, during true progression, and at the last visit. The patients were divided into 2 groups depending onconventional MRI suggests progression at 6 month or at 12 month. The APTw and apparent diffusion coefficient (ADC) values werecalculated for each tumor voxel. Changes in tumor volume, APTw, and ADC during the baseline to the initial follow up werecompared between progression and non-progression group, and then tested as predictors of OS, using Mann-Whitney U test andCox proportional hazards regression model.

RESULTS

The initial follow up was performed at 40 days (median). After bevacizumab, 12 patients showed progression at 6 month and 20patients showed progression at 12 months. Initial APTw decrease was pronounced in non-progression group compared toprogression group at either 6 month (average APTw decrease 0.396%; 95% confidence interval [CI] 0.24-0.92% in non-progressiongroup vs. 0.013%, 95% CI 0.063-0.38% in progression group, P =.04) or at 12 month (average 0.67%, 95% CI 0.378-1.173% vs.0.157%, 0.00-0.445%, P =.031). Initial ADC decrease or tumor volume decrease was not significantly different between the twogroups. No imaging predictor including initial and early reduction of APTw, ADC, and tumor volume, however, becomes a significantpredictor for OS.

CONCLUSION

Reduction in APTw signal can become an early imaging biomarker compared to diffusion-weighted imaging or tumor volume change,to predict short-term stability after anti-angiogenic treatment.


We recorded longitudinal MRI data of amide proton transfer-weighted and diffusion-weighted imaging and reported early change ofmolecular imaging can become an imaging biomarker for predicting treatment response in patients with recurrent glioblastoma. Useof this method will improve patient care by providing clinicians to better anticipate short-term outcome of patients.

ParticipantsCourtney A. Lawhn-Heath, MD, San Francisco, CA (Presenter) Nothing to DiscloseMiguel Hernandez Pampaloni, MD, San Francisco, CA (Abstract Co-Author) Nothing to DiscloseNicholas Fidelman, MD, San Francisco, CA (Abstract Co-Author) Research Grant, BTG International LtdRahul Aggarwal, San Francisco, CA (Abstract Co-Author) Nothing to DiscloseEmily Bergsland, MD, San Francisco, CA (Abstract Co-Author) Institutional research support, Lexicon Pharmaceuticals, IncInstitutional research support, Merck & Co, Inc Institutional research support, Novartis AG Consultant, Ipsen SA Consultant, Lexicon

Pharmaceuticals, Inc Thomas A. Hope, MD, San Francisco, CA (Abstract Co-Author) Research Grant, General Electric Company; Research Grant,Koninklijke Philips NV; Advisory Board, Ipsen SA; Researcher, Advanced Accelerator Applications SA

TEACHING POINTS

-In Peptide Receptor Radionuclide Therapy (PRRT), a radioligand targets cell membrane proteins to selectively internalize radiationto tumor cells. -In the NETTER-1 trial, Lu-177 DOTATATE was found to prolong progression-free survival in midgut neuroendocrinetumor (NET) patients, leading to FDA approval in January 2018. -Early retrospective trials have found high efficacy of 177Lu-PSMA-617 in castrate-resistant prostate cancer (CRPC) compared to other systemic therapies.


1. Introduction to theranostics a. Concept of using a molecule for both imaging and therapy b. Review existing theranostic agents2. Background on neuroendocrine tumors (NETs) a. Classification and types of NETs b. Existing treatments for NETs 3. Peptidereceptor radionuclide therapy (PRRT) in NETs a. Introduce DOTA-TATE and PRRT b. Review results of NETTER-1 trial c. Compareresults to previous non-randomized trials d. How is 177Lu-DOTA-TATE administered? e. Variations: 90Y vs. 177Lu, intra-arterial vs.intravenous, combination therapies 4. Background on castrate-resistant prostate cancer (CRPC) a. Disease characterization b.Existing therapies for CRPC and their efficacy 5. PRRT in CRPC a. Introduce PSMA and PRRT b. Review current early studies of177Lu-PSMA-617 c. Review possible future directions


ED015-MO

Molecular Imaging Monday Case of the Day

Monday, Dec. 2 7:00AM - 11:59PM Room: Case of Day, Learning Center



TEACHING POINTS



MSMI21A Molecular Imaging using Radioactive Tracers

MSMI21B Molecular Imaging with MRI and MRS

MSMI21C Molecular Imaging with Nanoparticles

MSMI21

Molecular Imaging Symposium: Basics of Molecular Imaging

Monday, Dec. 2 8:30AM - 10:00AM Room: S405AB

BQ MR MI NM US


ParticipantsZaver M. Bhujwalla, PhD, Baltimore, MD (Moderator) Nothing to DiscloseJan Grimm, MD,PhD, New York, NY (Moderator) Nothing to Disclose


[email protected]

Sub-Events

ParticipantsJan Grimm, MD,PhD, New York, NY (Presenter) Nothing to Disclose

LEARNING OBJECTIVES

1) Discuss the various radio tracers and their applications in Molecular Imaging studies. 2) Understand in which situations to usewhich radio tracers, what to consider when developing the imaging construct and what controls to obtain for nuclear imagingstudies. 3) Examples will contain imaging with small molecules, with antibodies and nanoparticles as well as with cells in order toprovide the participants with examples how o correctly perform their imaging studies. 4) Most of the examples will be from theoncology field but their underlying principles are universally applicable to other areas as well.

ParticipantsZaver M. Bhujwalla, PhD, Baltimore, MD (Presenter) Nothing to Disclose

LEARNING OBJECTIVES

1) To list the basic principles of magnetic resonance (MR) molecular imaging. 2) To describe the uses of noninvasive multi-nuclearMRI and magnetic resonance spectroscopic imaging (MRSI) for molecular imaging applications that provide spatial and temporalinformation on vasculature, metabolism and physiology. 3) To identify the applications of targeted MR contrast agents to detectreceptor and gene expression. 4) To describe strategies that combine detection with therapy for theranostic imaging and formetabolotheranostics. 5) To provide examples of translational applications of molecular imaging and theranostics.

ABSTRACT

Noninvasive multi-nuclear magnetic resonance (MR) imaging and spectroscopic imaging (MRSI) provide a wealth of spatial andtemporal information on vasculature, metabolism and physiology. Novel targeted contrast agents have widened the scope of MRtechniques for molecular imaging applications to detect receptor and gene expression. In cancer, molecular imaging can be appliedto identify targets specific to cancer with imaging, design agents against these targets to visualize their delivery, and monitorresponse to treatment, with the overall purpose of minimizing collateral damage. Genomic and proteomic profiling can provide anextensive 'fingerprint' of each tumor. With this cancer fingerprint, theranostic agents can be designed to personalize treatment forprecision medicine of cancer, and minimize damage to normal tissue.

ParticipantsHeike E. Daldrup-Link, MD, Palo Alto, CA (Presenter) Nothing to Disclose

LEARNING OBJECTIVES

1) To understand important safety aspects of ultrasmall superparamagnetic iron oxide nanoparticles (USPIO). 2) To understand thebiodistribution of ferumoxytol nanoparticles and implications for imaging diagnoses. 3) To recognize the value of ferumoxytolnanoparticles for cancer MR imaging and PET/MR imaging.

ABSTRACT

Gadolinium chelates as contrast agents for MRI have been associated with mounting concerns about nephrogenic sclerosis andgadolinium deposition in the brain. Therefore, a search for safe alternatives is currently underway. In North America, the ironsupplement ferumoxytol has gained considerable interest as an MR contrast agent. In Europe, ferumoxtran-10 is re-entering clinicaltrials. Both ferumoxytol and ferumoxtran-10 provide long-lasting blood pool enhancement, which can be used for MR imaging examsthat require detailed and/or long-lasting vessel delineation for MR angiographies, tissue perfusion studies, and whole body tumorstaging. Iron oxide nanoparticles are slowly phagocytosed by macrophages in the reticuloendothelial system, making them ideal forMR imaging detection of tumors in the liver, spleen, lymph nodes, and bone marrow. Similarly, iron oxide nanoparticles are slowlyphagocytosed by tumor-associated macrophages in cancers; which can be used to grade tumor-associated inflammation andmonitor the efficacy of new cancer immunotherapies. This presentation provides an introduction to the use of iron oxide

MSMI21D Ultrasound Molecular Imaging with Targeted Bubbles

MSMI21E Quantitative Imaging Biomarkers and Radiogenomics

nanoparticles for clinical MR and PET/MR imaging, including safety data acquired in children thus far, recent insights andmechanisms of rare, but potentially severe adverse reactions, applications that impact patient care and comparisons withgadolinium chelates. New developments for image guided therapy and theranostics are under way.

ParticipantsAlexander L. Klibanov, PhD, Charlottesville, VA (Presenter) Co-founder, Targeson, Inc, now dissolved; Shareholder, Targeson, Inc,now dissolved; Institutional research collaboration, AstraZeneca PLC; NIH Grant subcontract to UVA lab, SoundPipe Therapeutics;

LEARNING OBJECTIVES

1) Understand the principles of microbubble design-how to prepare fully biocompatible and safe ultrasound contrast agent particlesthat are clinically translatable, stable on storage, provide strong acoustic response and high sensitivity of detection by clinicalultrasound imaging systems, and could be targetable. 2) Understand the principles of selection of disease-specific targeting ligandsusable for contrast ultrasound imaging, based on receptor levels in the vasculature in the disease issues, as well as vascularbiomechanics. 3) Assess the results of early stage clinical trials performed with targeted microbubbles, and opportunities for clinicaltranslation in diagnostic imaging and image-guided interventions.

ABSTRACT

Ultrasound is the most widespread clinical imaging modality. Therefore, enabling molecular imaging potential in an ultrasound settingwill lead to the expanded and improved clinical diagnostic benefit. Ultrasound contrast microbubbles are already used in clinic asblood pool contrast agents, with excellent detection sensitivity: single particles with sub-picogram mass can be observed withclinical imaging systems in real time, at a depth of several cm. To achieve biomarker-selective molecular imaging, microbubble shellsurface is decorated with targeting ligand molecules (antibodies, peptides, carbohydrates) that assure selective binding andretention in the areas of disease. Clinical microbubbles are typically 1-3 um in diameter; they do not extravasate, so targetbiomarker receptors should be located on the luminal surface of vessel wall, e.g., vascular endothelium. Microbubbles are targetedto the biomarkers in the areas of inflammation and ischemia-reperfusion injury (P- and E-selectin, VCAM-1, ICAM-1) or to tumorneovasculature (VEGFR2). The latter, a heterodimeric peptide-targeted contrast microbubble from industry, has successfullycompleted Phase 1-2 clinical trials for imaging of ovarian, breast and prostate cancer lesions. Overall, targeted microbubblesempower molecular ultrasound imaging; they could also be used in conjunction with image-guided interventions, such as targetedbiopsy and therapy.

ParticipantsLawrence H. Schwartz, MD, New York, NY (Presenter) Nothing to Disclose


MSMI22A Hyperpolarized MRI of Cancer

MSMI22B Imaging of Delivered Gene Expression

MSMI22C PSMA Imaging in Prostate Cancer

MSMI22

Molecular Imaging Symposium: Oncologic MI Applications

Monday, Dec. 2 10:30AM - 12:00PM Room: S405AB

BQ GU MR MI OI



ParticipantsPeter L. Choyke, MD, Rockville, MD (Moderator) License agreement, Koninklijke Philips NV; Researcher, Koninklijke Philips NV; Licenseagreement, ScanMed; License agreement, Rakuten Medical; Researcher, Rakuten Medical; Researcher, General Electric Company;Researcher, Progenics Pharmaceuticals, Inc; Researcher, Novartis AG; ; ; ; ; Vikas Kundra, MD, PhD, Houston, TX (Moderator) Institutional license agreement, Introgen Therapeutics, Inc; Research Grant,General Electric Company


[email protected]

[email protected]

LEARNING OBJECTIVES

1) To understand current advances in PET molecular imaging and clinical applications. 2) To understand new applications ofadvanced MRI techniques. 3) To improve understanding of theranostic agents based on targeted imaging agents. 4) To improveunderstanding of imaging delivered gene expression.

Sub-Events

ParticipantsDaniel B. Vigneron, PhD, San Francisco, CA (Presenter) Research Grant, General Electric Company;


[email protected]

ParticipantsVikas Kundra, MD, PhD, Houston, TX (Presenter) Institutional license agreement, Introgen Therapeutics, Inc; Research Grant,General Electric Company


[email protected]

LEARNING OBJECTIVES

1) To improve understanding of imaging of delivered gene expression. 2) Multiple modalities and reporter systems will be discussed.

ParticipantsPeter L. Choyke, MD, Rockville, MD (Presenter) License agreement, Koninklijke Philips NV; Researcher, Koninklijke Philips NV; Licenseagreement, ScanMed; License agreement, Rakuten Medical; Researcher, Rakuten Medical; Researcher, General Electric Company;Researcher, Progenics Pharmaceuticals, Inc; Researcher, Novartis AG; ; ; ; ;


[email protected]

LEARNING OBJECTIVES

1) To understand the basic biology of PSMA and its role in prostate cancer. 2) To describe the sensitivity of PSMA PET with regardto other PET agents for prostate cancer. 3) To demonstrate potential pitfalls and unexpected findings with PSMA PET imaging.

ABSTRACT

PSMA PET imaging is a highly sensitive method of detecting prostate cancer. It can be used in the initial diagnosis and staging, forrecurrence and to assess metastatic disease. PSMA is expressed in aggressive cancers but not in low grade or highlyundifferentiated cancers. It is superior to all other PET agents in terms of sensitivity especially in the recurrence setting. It can beused to determine if lesions seen on CT or MRI are related to prostate cancer. Pitfalls include false negatives in highly aggressivedisease, the diagnosis of additional malignancies and false positives in the cisterna chyli and fibrous dysplasia. PSMA PET will have a

MSMI22D Gastrin Releasing Peptide Receptors: When in the Course of Prostate Cancer Will They Be Useful?

MSMI22E Iron Oxide Enhanced MR Imaging in GU Malignancies

profound impact on the management of prostate cancer.

ParticipantsAndrei Iagaru, MD, Emerald Hills, CA (Presenter) Research Grant, General Electric Company Research Grant, ProgenicsPharmaceuticals, Inc Research Grant, Advanced Accelerator Applications SA

LEARNING OBJECTIVES

1) List some of the radiopharmaceuticals targeting gastrin-releasing peptide receptors that are used in prostate cancer. 2)Understand underlying biology and mechanism of action for the radiopharmaceuticals targeting gastrin-releasing peptide receptors inprostate cancer. 3) Discuss patterns of prostate cancer appearance when using the radiopharmaceuticals targeting gastrin-releasing peptide receptors.

ABSTRACT

Various radiopharmaceuticals targeting different molecules have been studied in prostate cancer (PC). One recent class of tracersare the gastrin releasing peptide (GRP) analogs. Bombesin (BBN) is analog to the mammalian GRP, and it binds with high affinity toits transmembrane receptors, the GRP receptors (GRPR). Preclinical evaluation in PC cells and animal models have reportedencouraging results; therefore, they are currently investigated as targets both for PC imaging and therapy. Increases in GRPRexpression have been shown in 63-100% of intraprostatic PC, and 50-80% of nodal and osseous metastases. High densityexpression of GRPR has been reported in primary PC in contrast to surrounding healthy tissues and hyperplastic prostate, allowingfor detection of early neoplastic events in the prostate with high specificity.

ParticipantsBaris Turkbey, MD, Bethesda, MD (Presenter) Research support, Koninklijke Philips NV; Royalties, Invivo Corporation; Investigator,NVIDIA Corporation


[email protected]

LEARNING OBJECTIVES

1) Understand mechanism of iron-oxide enhanced MRI. 2) Understand imaging findings of iron-oxide enhanced MRI. 3) Understandpitfalls and limitations of iron-oxide enhanced MRI.

ABSTRACT

n/a


MI204-SD-MOA1

Comparison of Metabolic Changes in the Liver with Hepatitis B Virus Infection and Fibrotic ChangeUsing in Vivo Hyperpolarized 13C MR Spectroscopy: A Preliminary Study

Station #1

MI205-SD-MOA2

Effect of Tract Ablation to Reduce Viable Tumor Cell Adhering in the Electrode After RadiofrequencyAblation for Tumor

Station #2

MIS-MOA

Molecular Imaging Monday Poster Discussions

Monday, Dec. 2 12:15PM - 12:45PM Room: MI Community, Learning Center

MI


ParticipantsPedram Heidari, MD, Charlestown, MA (Moderator) Nothing to Disclose

Sub-Events

ParticipantsSeungwon Oh, Gwangju, Korea, Republic Of (Presenter) Nothing to DiscloseSang Soo Shin, MD, Gwangju, Korea, Republic Of (Abstract Co-Author) Nothing to DiscloseSung Mo Kim, Jellanamdo, Korea, Republic Of (Abstract Co-Author) Nothing to DiscloseJong Eun Lee, Gwangju, Korea, Republic Of (Abstract Co-Author) Nothing to DiscloseChung Man Moon, Gwangju, Korea, Republic Of (Abstract Co-Author) Nothing to DiscloseYong-Yeon Jeong, MD, Gwangju, Korea, Republic Of (Abstract Co-Author) Nothing to Disclose


[email protected]

PURPOSE

The purpose of this study was to compare the cellular metabolic changes in the liver with HBV infection and fibrotic change using invivo hyperpolarized 13C MR spectroscopy (MRS).


Animal models with HBV infection (n = 2) without fibrotic change and advanced hepatic fibrosis (n = 2) were induced in the mice byHBV and thioacetamide (TAA) injection, respectively. Also, normal controls (n = 2) were injected with PBS (7.4 pH) simultaneouslyby the intraperitoneal route. HyperSense DNP polarizer was used to hyperpolarize [1-13C] pyruvate (Pyr), and the real time 13CMRS was performed on the mouse liver following an injection of hyperpolarized [1-13C] Pyr.

RESULTS

A real time in vivo hyperpolarized 13C dynamic MRS demonstrated differential patterns of metabolic changes in the liver with HBVinfection and fibrotic change, compared with normal liver. The ratios of [1-13C] lactate (Lac)/Pyr and [1-13C] alanine (Ala)/Pyrwere significantly higher in hepatic fibrosis group than in normal and HBV groups (P < 0.001). Also, [1-13C] Lac/Pyr and [1-13C]Ala/Pyr in HBV group were significantly higher than in normal group (P < 0.001).

CONCLUSION

It is assumed that significant increases of [1-13C] Lac and [1-13C] Ala would be closely related to the progression of hepaticfibrosis. Further, the levels of [1-13C] Lac and [1-13C] Ala could be potentially considered as important biomarkers for the earlydiagnosis of hepatic fibrosis in patients with HBV infection.


In vivo 13C-MRS might be potentially useful for noninvasive diagnosis and monitoring of patients with HBV infection regarding theprogression to hepatic fibrotic change.

ParticipantsSu Jung Ham, Seoul, Korea, Republic Of (Presenter) Nothing to DiscloseHwon Heo, Seoul, Korea, Republic Of (Abstract Co-Author) Nothing to DiscloseYeon Ji Chae, Seoul, Korea, Republic Of (Abstract Co-Author) Nothing to DiscloseKyung Won Kim, MD, Seoul, Korea, Republic Of (Abstract Co-Author) Nothing to Disclose

PURPOSE

Radiofrequency ablation (RFA) is curative treatment methods for hepatic tumor, but tumor implantation at the needle tract is well-known complication. We aimed to evaluate the effect of tract ablation to minimize the number of viable tumor cell exposed in theneedle after RFA using animal tumor model and live cell counting method.


Hep3B-Luc cells were engrafted into Balb/c-nude mice. The mice whose tumor reached 10 mm in long diameter were selected and

MI112-ED-MOA3

Superparamagnetic Iron Oxide Nanoparticles: Applications and Developments in Diagnostics andTherapy

Station #3

randomly assigned for three groups: Needle only (needle placement without RFA, n=10), RFA only (needle placement with RFA,n=11), RFA-TA (needle placement with RFA and tract ablation, n=10) groups. An internally cooled, 17-gauge RFA needle with a 10-mm active tip was used. Tumor RFA was performed for 1 minute at the 5 watt using pump cooling mode. Tract ablation wasperformed using 5 watt using non-cooling mode until the temperature reached 80-100 ?. The viability and viable cell numbers ofadherent tumor cells at the RFA needle were evaluated by using the IVIS spectrum and live cell counting method with acridineorange/propidium iodide stain.

RESULTS

The BLI signals significantly differed between groups (needle only group, 8.2 M ± 7.0; RFA only group, 13.3 M ± 15.7; RFA-TAgroup, 3.9M ± 3.5, p=0.007). Host-hoc study revealed the difference occurred between RFA only group and RFA-TA group(p=0.049). The counted viable cell numbers also significantly differed between groups (needle only group, 20.8 ± 23.7; RFA onlygroup, 305.9 ± 344.1; RFA-TA group, 3.0 ± 2.7, p=0.003). Host-hoc study revealed the difference occurred between RFA onlygroup and RFA-TA group (p=0.002) and between RFA only group and needle only group (p=0.004).

CONCLUSION

Tract ablation greatly reduced the adherent viable tumor cells at the needle after performing RFA.


We provided direct evidence that tract ablation greatly reduce the risk of tract seeding after RFA. We propose to incorporate tractablation as a routine procedure in all liver tumor RFA.

ParticipantsHarald Ittrich, MD, Hamburg, Germany (Presenter) Nothing to DiscloseKersten Peldschus, MD, Hamburg, Germany (Abstract Co-Author) Nothing to DiscloseMichael G. Kaul, Hamburg, Germany (Abstract Co-Author) Nothing to DiscloseNina Raabe, MD, Hamburg, Germany (Abstract Co-Author) Nothing to DiscloseCaroline Jung, Hamburg, Germany (Abstract Co-Author) Nothing to DiscloseGerhard B. Adam, MD, Hamburg, Germany (Abstract Co-Author) Nothing to Disclose


[email protected]

TEACHING POINTS

• SPIO can be used for diagnosis in MRI • Monodisperse SPIO improve physicochemistry and pharmacodynamics • SPIO in targetedprobes can be used in in vitro diagnostic imaging (μNMR) • The potential of SPIO in magnetic particle imaging (MPI) must beevaluated.


Superparamagnetic iron oxide nanoparticles (SPIO) can be used to image tumors and metastases in the liver, spleen and bonemarrow, lymph nodes and the CNS, MRA and perfusion imaging. Experimental approaches describe SPIO accumulationin inflammation,tumors and macrophages, atheroscrerotic lesions and of SPIO ligands in tumor endothelia and tumor cells, areas of apoptosis,infarction, inflammation and degeneration in cardiovascular and neurological diseases. Labeling of stem or immune cells allows thevisualization of cell therapies or transplant rejections. SPIO coupling to ligands, radio- and/or chemotherapeutics, embedding incarrier systems or activatable smart sensor probes enable molecular tumor therapies or the imaging of metabolic and enzymaticprocesses. Monodisperse SPIO will improve SPIO-based MRI in the future and targeted probes in DMR using chip-based μNMR mayexpand the spectrum of in vitro analysis. Magnetic particle imaging (MPI) as a new imaging modality offers new applications forSPIO in cardiovascular and interventional diagnostics and therapy.


MI206-SD-MOB1

Simultaneous Measurement of Split Renal Glomerular Filtration Rate, Effective Renal Plasma Flow andRegional Quantitative Imaging Using Model Analysis of Dynamic Area Detector CT Images

Station #1

MI113-ED-MOB3

A Beginner's Guide to [177Lu]DOTATATE Peptide Receptor Radionuclide Therapy

Station #3

MIS-MOB

Molecular Imaging Monday Poster Discussions

Monday, Dec. 2 12:45PM - 1:15PM Room: MI Community, Learning Center

MI


ParticipantsPedram Heidari, MD, Charlestown, MA (Moderator) Nothing to Disclose

Sub-Events

ParticipantsTakashi Ichihara, PhD, Toyoake, Japan (Presenter) Research Grant, 12Sigma TechnologiesRyoichi Kato, MD, Toyoake, Japan (Abstract Co-Author) Nothing to DiscloseRyo Matsukiyo, Toyoake, Japan (Abstract Co-Author) Nothing to DiscloseTatsuto Oshima, Toyoake, Japan (Abstract Co-Author) Nothing to DiscloseMidori Hasegawa, Toyoake, Japan (Abstract Co-Author) Nothing to DiscloseRyoichi Shiroki, Toyoake, Japan (Abstract Co-Author) Nothing to DiscloseTakashi Kenmochi, Toyoake, Japan (Abstract Co-Author) Nothing to DiscloseShigeki Kobayashi, MD, Toyoake, Japan (Abstract Co-Author) Nothing to DiscloseHiroshi Toyama, Toyoake, Japan (Abstract Co-Author) Nothing to Disclose

PURPOSE

The purpose of this study was to simultaneously measure split renal glomerular filtration rate (GFR) and effective renal plasma flow(ERPF) and generate their distribution images based on compartment model analysis using dynamic area detector CT (ADCT).


Seventeen living-related renal transplant donors underwent the inulin clearance test and standard renal dynamic CT scan for 3D-CTangiography with addition of low radiation dose dynamic scan using 320-row ADCT (Aquilion ONE; Canon Medical Systems). As theinput function, time-density curves (TDCs) were obtained from the left and right renal arteries. The output functions were obtainedfrom a pixel in the renal cortex and medulla of the left and right kidney. These TDCs were employed for calculation of the regionalGFR and ERPF on a pixel-by-pixel basis on compartment analysis. In our proposed compartment analysis, arterial blood (plasma),extravascular space of kidney and glomerulus were defined as an individual compartment. K1 and k2 represent the first-ordertransfer constants from plasma to extravascular space and from extravascular to plasma, respectively. The elimination of themarker from the body is from plasma. K3(=GFR) represents transfer constants of this elimination. The total GFR and ERPF werecalculated from integration of the regional GFR and ERPF over the whole kidney. Total GFR was compared with the results of inulinclearance test.

RESULTS

Regional and total GFR and ERPF were obtained in all subjects. The results of a linear regression analysis between the CT based GFRand inulin clearance showed a good correlation (y = 0.969x + 2.73, r = 0.761, p = 0.00039).

CONCLUSION

We have developed a new functional imaging to simultaneously measure GFR and ERPF and generate their distribution images basedon compartment model analysis by using dynamic ADCT.


This approach would contribute substantially to understanding of a variety of renal disease mechanisms, as well as potentiallyincreasing the accuracy of diagnosis and directing appropriate therapy.

ParticipantsSamuel J. Galgano, MD, Birmingham, AL (Presenter) Research support, Blue Earth Diagnostics Ltd; Research support, AdvancedAccelerator Applications SACharlies Xie, MD, Birmingham, AL (Abstract Co-Author) Nothing to DiscloseGagandeep Choudhary, MD, MBBS, Homewood, AL (Abstract Co-Author) Nothing to DiscloseJonathan E. McConathy, MD, PhD, Birmingham, AL (Abstract Co-Author) Research Consultant, Eli Lilly and Company; ResearchGrant, Eli Lilly and Company; Research Consultant, Blue Earth Diagnostics Ltd; Research Grant, Blue Earth Diagnostics Ltd; ResearchConsultant, General Electric Company; Spouse, Research Consultant, Alphasource; Spouse, Research Grant, NavideaBiopharmaceuticals, Inc; Spouse, Research Grant, AbbVie Inc


[email protected]

TEACHING POINTS

• [177Lu]DOTATATE therapy is FDA-approved for treatment of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) • Acomprehensive patient work-up prior to therapy is essential, including history and physical, assessment of renal, hepatic, andhematopoietic function, and pretreatment [68Ga]DOTATATE PET scan • Close collaboration with medical and surgical oncologists isnecessary to manage patients who are eligible and/or undergoing evaluation for [177Lu]DOTATATE therapy • Following initiation of[177Lu]DOTATATE therapy, intermittent assessment of renal, hepatic, and hematopoietic function is needed to assess for toxicities


• Introduction and Background • Considerations in Pretreatment Patient Assessment o Imaging with [68Ga]DOTATATE: Who toImage? o Pretreatment History and Physical o Pretreatment Laboratory Assessments • Developing a Multidisciplinary NeuroendocrineTumor Service • Administration of [177Lu]DOTATATE: Potential Pitfalls and Adverse Events • Treatment Schedule and Follow-up ofPatients After [177Lu]DOTATATE


MSMI23A New Radiotracers for Molecular Imaging of the Brain

MSMI23B Brain MI in Dementia

MSMI23C Molecular Imaging of Parkinsonism

MSMI23D Machine Learning in Brain MI

MSMI23

Molecular Imaging Symposium: Neurologic MI Applications

Monday, Dec. 2 1:30PM - 3:00PM Room: S405AB

AI MI NR



ParticipantsAlexander Drzezga, MD, Cologne, Germany (Moderator) Research support, Siemens AG; Speakers Bureau, Siemens AG; Stockholder,Siemens AG; Research support, General Electric Company; Consultant, General Electric Company; Research support, Life MolecularImaging; Speakers Bureau, sanofi-aventis Group; Speakers Bureau, General Electric Company; Research support, Eli Lilly andCompany; Satoshi Minoshima, MD, PhD, Salt Lake City, UT (Moderator) Consultant, Hamamatsu Photonics KK; Research Grant, Hitachi, Ltd;Research Grant, Nihon Medi-Physics Co, Ltd;


[email protected]

Sub-Events

ParticipantsPeter Herscovitch, MD, Bethesda, MD (Presenter) Nothing to Disclose


[email protected]

LEARNING OBJECTIVES

1) Describe new radiotracers and their targets for molecular imaging (MI) of the brain. 2) Understand how new molecular imagingradiotracers are used to study the pathophysiology of neuropsychiatric diseases. 3) Understand the U.S. FDA and Medicareapproval process for new radiotracers for molecular brain imaging.

ParticipantsAlexander Drzezga, MD, Cologne, Germany (Presenter) Research support, Siemens AG; Speakers Bureau, Siemens AG; Stockholder,Siemens AG; Research support, General Electric Company; Consultant, General Electric Company; Research support, Life MolecularImaging; Speakers Bureau, sanofi-aventis Group; Speakers Bureau, General Electric Company; Research support, Eli Lilly andCompany;

LEARNING OBJECTIVES

1) Understand the molecular targets available for imaging of presynaptic dopaminergic synapses. 2) Appreciate the diagnosticcharacteristics of dopamine transporter imaging in movement disorder syndromes. 3) Master the appropriate use settings for clinicalapplication of dopamine transporter imaging. 4) Appreciate alternative molecular imaging approaches that may offer value indistinction between movement disorders in the future.

ParticipantsKirk A. Frey, MD, PhD, Ann Arbor, MI (Presenter) Consultant, MIM Software Inc; Stockholder, General Electric Company;Stockholder, Johnson & Johnson; Stockholder, Novo Nordisk AS; Stockholder, Bristol-Myers Squibb Company; Stockholder, Merck &Co, Inc;

LEARNING OBJECTIVES

1) Gain insights on available methods of molecular imaging in dementia and their significance. 2) Gain insights in principles and valueof dopaminergic imaging in Parkinsonian syndromes. 3) Gain understanding in approval processes for new brain molecular imagingtracers and ongoing clinical trials.

ParticipantsSatoshi Minoshima, MD, PhD, Salt Lake City, UT (Presenter) Consultant, Hamamatsu Photonics KK; Research Grant, Hitachi, Ltd;Research Grant, Nihon Medi-Physics Co, Ltd;


MSMI24A What is 'Theranostics'?

MSMI24B Practical Aspects of Theranostics Implementation

MSMI24

Molecular Imaging Symposium: MI Theranostics

Monday, Dec. 2 3:30PM - 5:00PM Room: S405AB

MI



ParticipantsMunir Ghesani, MD, West Windsor, NJ (Moderator) Author, Siemens AG; Speaker, Siemens AGDaniel Pryma, MD, Philadelphia, PA (Moderator) Research Grant, Siemens AG; Research Grant, 511 Pharma; Research Grant,Progenics Pharmaceuticals, Inc; Research Consultant, Progenics Pharmaceuticals, Inc; Research Consultant, 511 Pharma; ResearchConsultant, Actinium Pharmaceuticals, Inc; Research Consultant, Nordic Nanovector ASA

Sub-Events

ParticipantsMunir Ghesani, MD, West Windsor, NJ (Presenter) Author, Siemens AG; Speaker, Siemens AG


[email protected]

LEARNING OBJECTIVES

1) Understand the basic principle of theranostics. While the theranostic concept is decades old, applied in clinical practice first inform of radioiodine in diagnosis and treatment of thyroid cancer, recent FDA approval of a theranostic pair and its successfulintegration in clinical practice has made it very clear that this it will be widely applied in the clinical management of variousmalignancies in the future. 2) This course will provide information about the basic principle, current practice and future promise oftheranostics.

ABSTRACT

Understand the basic principle of theranostics. While the theranostic concept is decades old, applied in clinical practice first in formof radioiodine in diagnosis and tratment of thyroid cancer, recent FDA approval of a theranostic pair and its successful integrationin clinical practice has made it very clear that this it will be widely applied in the clinical management of various malignancies in thefuture. This course will provide information about the basic principle, current practice and future promise of theranostics.

ParticipantsDaniel Pryma, MD, Philadelphia, PA (Presenter) Research Grant, Siemens AG; Research Grant, 511 Pharma; Research Grant,Progenics Pharmaceuticals, Inc; Research Consultant, Progenics Pharmaceuticals, Inc; Research Consultant, 511 Pharma; ResearchConsultant, Actinium Pharmaceuticals, Inc; Research Consultant, Nordic Nanovector ASA

LEARNING OBJECTIVES

1) To understand the regulatory requirements for the implementation of new diagnostic and therapeutic radiopharmaceuticals. 2) Toappreciate the physical space needed to safely administer such radiopharmaceuticals. 3) To review the resources needed to assessand follow patients considered for treatment with radiopharmaceuticals.

ABSTRACT

There is a great deal of growth in therapeutic radiopharmaceuticals and associated companion diagnostics. Administering theseagents requires specific training, regulatory approvals, medical and financial considerations as well as appropriate physical space.We will review these aspects to help the attendee understand the steps needed to permit optimal inclusion of these new agentsinto one's practice.


ED015-TU

Molecular Imaging Tuesday Case of the Day

Tuesday, Dec. 3 7:00AM - 11:59PM Room: Case of Day, Learning Center



TEACHING POINTS



RC317A Introduction to Imaging in Prostate Cancer

RC317B Next Generation Prostate MRI

RC317C Molecular Prostate Imaging: Chemistry to Clinic

RC317

Emerging Technologies: Prostate Cancer Imaging & Management - Update 2019

Tuesday, Dec. 3 8:30AM - 10:00AM Room: S505AB

GU MI MR NM



ParticipantsPeter L. Choyke, MD, Rockville, MD (Moderator) License agreement, Koninklijke Philips NV; Researcher, Koninklijke Philips NV; Licenseagreement, ScanMed; License agreement, Rakuten Medical; Researcher, Rakuten Medical; Researcher, General Electric Company;Researcher, Progenics Pharmaceuticals, Inc; Researcher, Novartis AG; ; ; ; ;


[email protected]

LEARNING OBJECTIVES

1) Understand current issues in prostate cancer relevant to imaging. 2) Understand the role of emerging technologies in the imagingand management of prostate cancer.

ABSTRACT

Prostate cancer is a major health issue. Imaging has made great strides in the last decade including the use of multiparametric MRI,MR-ultrasound fusion biopsies and most recently PET scanning. This refresher course explores emerging technolgies in prostatecancer imaging and management.

Sub-Events

ParticipantsPeter L. Choyke, MD, Rockville, MD (Presenter) License agreement, Koninklijke Philips NV; Researcher, Koninklijke Philips NV; Licenseagreement, ScanMed; License agreement, Rakuten Medical; Researcher, Rakuten Medical; Researcher, General Electric Company;Researcher, Progenics Pharmaceuticals, Inc; Researcher, Novartis AG; ; ; ; ;


[email protected]

LEARNING OBJECTIVES

1) Understand the impact of new screening guidelines on imaging of prostate cancer. 2) Understand the issues facing clinicianstreating prostate cancer.

ABSTRACT

This talk will provide an overview regarding the major issues of imaging in prostate cancer including screening and detection, initialstaging, biochemical recurrence and metastatic disease. Recent trends in the management of prostate cancer from activesurveillance to first and second line androgen deprivation, radium and chemotherapy/immunotherapy will be briefly discussed. Therole of imaging in prostate cancer is becoming much more central than it was a decade ago and this talk will set the stage for othertalks in the session that will provide new details regarding novel imaging methods.

ParticipantsBaris Turkbey, MD, Bethesda, MD (Presenter) Research support, Koninklijke Philips NV; Royalties, Invivo Corporation; Investigator,NVIDIA Corporation


[email protected]

LEARNING OBJECTIVES

1) Understand current status and uses of multi-parametric MRI. 2) Understand role of MRI in assessment of prostate canceraggressiveness and tumor heterogeneity. 3) Understand role of computer aided diagnosis systems in evaluation of prostate canceraggressiveness and tumor heterogeneity.

ParticipantsMartin G. Pomper, MD, PhD, Baltimore, MD (Presenter) Research Grant, Progenics Pharmaceuticals, Inc; Royalties, ProgenicsPharmaceuticals, Inc

RC317D Hyperpolarized C-13 MR Molecular Imaging of Prostate Cancer

RC317E Radionuclide Therapy for Prostate Cancer


[email protected]

LEARNING OBJECTIVES

1) To compare and contrast the imaging characteristics of present and emerging molecular imaging agents for prostate cancer. 2)To describe how emerging molecular imaging agents for prostate cancer are being integrated into clinical practice. 3) To focus onPET agents targeting the prostate-specific membrane antigen (PSMA) with respect to a new structured reporting system proposedto enhance clinical management.

ABSTRACT

n/a

ParticipantsDaniel B. Vigneron, PhD, San Francisco, CA (Presenter) Research Grant, General Electric Company;

LEARNING OBJECTIVES

1) To describe the basic principles and techniques used in hyperpolarized carbon-13 MRI. 2) Understand the cellular metabolicreprogramming that occurs in prostate cancer. 3) Demonstrate the changes in pyruvate to lactate conversion that are observed inprostate cancer and differences with cancer aggressiveness and response to therapy.

ParticipantsFrank I. Lin, MD, Bethesda, MD (Presenter) Nothing to Disclose


[email protected]


SSG07-01 Targeted Delivery of Bismuth-Based Nanoparticles for the Diagnosis of Liver Fibrosis via Spectral CT


SSG07-02 Stem Cell Labeling and Tracking Using Mechanoporation


SSG07

Molecular Imaging (New Tracers and Alternative Imaging Modalities)

Tuesday, Dec. 3 10:30AM - 12:00PM Room: S505AB

MI



ParticipantsGabriel C. Fine, MD, Salt Lake City, UT (Moderator) Nothing to DiscloseGerard N. Bischof, PhD, Cologne, Germany (Moderator) Nothing to Disclose

Sub-Events

AwardsTrainee Research Prize - Medical Student

ParticipantsShiman Wu, Shanghai, China (Presenter) Nothing to DiscloseXianfu Meng, Shanghai, China (Abstract Co-Author) Nothing to DiscloseWenbo Bu, Shanghai, China (Abstract Co-Author) Nothing to DiscloseZhenwei Yao, Shanghai, China (Abstract Co-Author) Nothing to Disclose


[email protected]

PURPOSE

Early diagnosis of liver fibrosis is essential to prevent progression to cirrhosis. However, there is currently few effective medicalimaging technique to accurately diagnose it. This study assesses the potential utility of targeting nanoparticles, BaBiF5@PDA@HA,as contrast agents for gemstone spectral computed tomography (GSCT) in the diagnosis of liver fibrosis.


BaBiF5 nanoparticles were synthesized and transformed to be hydrophilic with polydopamine (PDA). Then hyaluronic acid (HA)derivatives, target-specific biomarkers for liver fibrosis, were conjugated onto the nanoparticles. The resulting BaBiF5@PDA@HAnanoprobes were further applied as contrast agents for GSCT. The CT Hounsfield unit (HU) value was measured on monochromaticimages (40 to 140 keV ) acquired by GSCT for experimental group for liver fibrosis mice models(induced by 8-week MCD diet), andsham mice group(regular diet). Resulting data were compared using Student-t and Mann-Whitney tests. All animal experiments wereperformed following protocols approved by the institutional animal care and use committee. Sirius red staining were performed forhistopathological assessment.

RESULTS

After BaBiF5@PDA@HA nanoparticles were injected , the CT value of liver was significantly greater (P < .0001) in experimentalgroup than in sham group from10 minutes to 80 minutes. The maximal difference of the liver CT value between two groups wasobserved 30 minutes after the injection (88.33±11.00 HU vs 47.78±3.53 HU), as a result of accumulation of BaBiF5@PDA@HA in thefibrosis zone of experimental group. Moreover, in the experimental group ,the spectral HU curve of liver analyzed at post-30 minutesindicated that the CT value of liver increased as the monochromatic energy level decreased. Such a characteristic of X-rayattenuation endowed BaBiF5@PDA@HA with comparatively potential for liver fibrosis diagnosis, in lower monochromatic energyimages. Thus, monochromatic energy level at 40 keV increased detection sensitivity by revealing highest CT value (130.67±13.96HU). Additionally, the area of liver fibrosis was more visible and closer to pathological results on 40keV monochromatic images.

CONCLUSION

BaBiF5@PDA@HA nanoparticles, as GSCT contrast agents, were successfully used to detect liver fibrosis.


GSCT employing targeted bismuth-based nanoparticles may improve the early noninvasive diagnosis of liver fibrosis.

ParticipantsHossein Nejadnik, MD, PhD, Stanford, CA (Presenter) Nothing to DiscloseAshok Joseph Theruvath, MD, Stanford, CA (Abstract Co-Author) Nothing to DiscloseAnna Liu, Atlanta, GA (Abstract Co-Author) Nothing to Disclose

SSG07-03 Ultrasmall Hybrid Protein-Copper Sulfide Nanoparticles Targeting Photoacoustic Image with a HighSignal-to-Noise Ratio for Orthotopic Hepatocellular Carcinoma


Wei Wu, Stanford, CA (Abstract Co-Author) Nothing to DiscloseGang Ren, MD, PhD, San Francisco, CA (Abstract Co-Author) Nothing to DiscloseTodd Sulchek, Atlanta, GA (Abstract Co-Author) Nothing to DiscloseHeike E. Daldrup-Link, MD, Palo Alto, CA (Abstract Co-Author) Nothing to Disclose

PURPOSE

Until now, the only ways of labeling adipose fat derived stem cells (ADSC) for in vivo imaging have required manipulation of the cellsin the laboratory. In a clinical setting, ADSC are harvested and transplanted within one surgery. To provide instant iron labeling, wetested the ability of a new microfluidic device to label ADSC with ferumoxytol nanoparticles within 15 minutes or less such that thelabeled cells can be detected with magnetic resonance imaging (MRI) and magnetic particle imaging (MPI).


Studies were performed with a custom-designed microfluidic device, which contains ridges to compress ADSC during their devicepassage. Cell relaxation after compression leads to cell volume exchange for convective transfer of nanoparticles and nanoparticleuptake into the cell. ADSCs were passed through our ferumoxytol-doped microfluidic device and the cellular iron uptake wasevaluated by DAB-Prussian blue, fluorescent microscopy, and inductively coupled plasma spectrometry (ICP). To evaluate theeffect of mechanoporation on MR signal, labeled and unlabeled ADSCs were imaged in vitro as well as ex vivo in pig knee specimenby MRI and MPI. T2 relaxation times and iron concentrations calculated by MPI were compared between labeled and unlabeled celltransplants using Student T-test with p<0.05.

RESULTS

DAB-Prussian blue, flourescent microscopy, and flowcytometry analysis demonstrated labeling efficiency of more than 95% of theADSCs. ICP results showed iron uptake of more than one pg per cell in the labeling group. Ferumoxytol labeled ADSCs revealedsignificantly shorter T2 relaxation times (24.2±2.1 ms) compared to unlabeled cells (79.5±0.8 ms) on MRI (p<0.05). Afterimplantation of the ADSCs into pig knee, labeled implants demonstrated significantly higher iron concentration (1.13±0.07 ug)compared to unlabeled cells (0.008±0.003 ug) on MPI and significantly shorter T2 relaxation times (33±6.2 ms) compared tounlabeled group (102.7±5.9 ms) (p<0.05).

CONCLUSION

Mechanoporation provided instant ferumoxytol labeling of ADSC within 15 minutes or less such that the labeled cells can bedetected with MRI and MPI.


Mechanoporation represents a new, fast, and readily clinically translatable method for labeling therapeutic cells with ferumoxytol.This facilitates iron labeling approaches for in vivo tracking of therapeutic cells with MRI and MPI.

ParticipantsZhang Hai, MD, Shen Zhen, China (Presenter) Nothing to DiscloseYing Li, Shen Zhen, China (Abstract Co-Author) Nothing to Disclose


[email protected]

PURPOSE

Although photoacoustic imaging combined with second near infrared (NIR II) molecular probes for tumor diagnosis has drawntremendous attention during the past few decades, the targeted photoacoustic imaging of orthotopic hepatocellular carcinoma (O-HCC) still remains a challenge due to high liver vascularization and non-specificity of probes in liver tumors.


We report on cyclic arginine-glycine-aspartic acid (cRGD) peptide conjugated ultrasmall CuS@BSA-RGD NPs which encapsulatebovine serum albumin (BSA) and possess high optical absorption at 1064 nm. The encapsulation of BSA results in greatbiocompatibility of the NPs along with excellent photostability and physiological stability. The cRGD conjugation enables theimprovement of tumor uptake of the NPs by virtue of its positive tumor cell targeting capability.

RESULTS

Ultrasmall CuS@BSA-RGD NPs were successfully synthesized for the photoacoustic imaging of targeted O-HCC. The NPs exhibitedstrong absorbance in the NIR II wavelengths. photoacoustic imaging in deep tissue areas with a lower background was achievedbecause the biological tissues show low optical absorption and photon scattering at the NIR II window, The efficient accumulationof the NPs in the tumor over time after intravenous administration to O-HCC bearing mice was achieved, which resulted in highlysensitive photoacoustic visualization. the active tumor targeting capability of the NPs enables them to accumulate significantly inthe tumor region. and the O-HCC region showed significantly enhanced photoacoustic signals (consequently much higher SNR)compared to that of the normal liver tissue. in addition, the NPs were non-toxic both in vitro and in vivo.

CONCLUSION

The first time validation of the CuS@BSA-RGD NPs for targeting photoacoustic imaging of the O-HCC model revealed its greatpotential for highly sensitive and accurate HCC detection in future translational medicine.


A targeted, highly effective and safe photoacoustic imaging were constructed by using the advantages of (NIR II). the teamstudied the CuS-NPs and image noise reduction,cutting and despecking , Research aim to explore theperforming fusion molecularimaging and promote deep cancer integrating diagnosis, targeted hybrid protein-CuS NPs which are for the first time, applied for

SSG07-04 Near-Infrared Fluorescence Labeled Anti-PD-L1-mAb For Tumor Imaging in Human Colorectal CancerXenografted Mice


SSG07-05 The Accumulation of Tumor-Derived Exosomes Can be Visualized by Molecular Imaging and Leads toChanges in the Immune Cell Composition in Target Sites of Metastasis


photoacoustic imaging of O-HCC with a high signal-to-noise ratio, has important clinical prospects and significance.

ParticipantsHuijie Jiang, PhD, MS, Harbin, China (Abstract Co-Author) Nothing to DiscloseMingyu Zhang, PhD, harbin, China (Presenter) Nothing to Disclose


[email protected]

PURPOSE

Our objective of this study was to develop a non-invasive imaging technique to monitor the dynamic changes in PD-L1 expression inCRC tumor.


The expression levels of PD-L1 in different CRC cell lines in vitro (SW620, SW480 and HCT8) were detected by FACS analysis andWestern blot assay. Subsequently, we labeled an anti-PD-L1 monoclonal antibody with near-infrared (NIR) dye and tested theability of the NIR-PD-L1-mAb probe to monitor PD-L1 expression in CRC-xenografted mice by performing optical imaging. Finally,based on the best time of in vivo imaging, different freshly dissected tissues were quantified by optical imaging for bio-distributionstudy.

RESULTS

The final protein concentration of NIR-PD-L1-mAb was 47.9 μg/ml and the dye/protein ratio was 1.954. SW620, SW480 and HCT8cell lines showed positive expression of PD-L1, the expression level of PD-L1 in SW620 cells was significantly higher as compared toSW480 or HCT8 cell cells. Our in vivo imaging showed the highest fluorescence signal of the xenografted tumors in mice bearingSW620 CRC cells, followed by tumors derived from SW480 and HCT8 cell lines. We detected the highest fluorescent intensity of thetumor at 120 hours after injection of NIR-PD-L1-mAb. The highest fluorescence intensity was seen in the tumor, followed by thespleen and the liver in SW620 xenografted mice. In SW480 and HCT8 xenografted mice, however, the highest fluorescent signalswere detected in the spleen, followed by the liver and the tumor.

CONCLUSION

Our findings indicate that SW620 cells express a higher level of PD-L1 among those three types of CRC cells, and the NIR-PD-L1-mAb binding to PD-L1 on the surface of CRC cells was specific. The technique was safe and could provide valuable information onPD-L1 expression of the tumor for development of therapeutic strategy of personized targeted immunotherapies as well astreatment response of CRC patients.


The technique was safe and could provide valuable information on PD-L1 expression of the tumor for development of therapeuticstrategy of personized targeted immunotherapies as well as treatment response of CRC patients.

ParticipantsMirjam Gerwing, MD, Muenster, Germany (Abstract Co-Author) Nothing to DiscloseVanessa Kocman, Muenster, Germany (Abstract Co-Author) Nothing to DiscloseMichel Eisenblaetter, MD,PhD, Muenster, Germany (Presenter) Nothing to DiscloseMoritz Wildgruber, MD, PhD, Iffeldorf, Germany (Abstract Co-Author) Nothing to DiscloseWalter L. Heindel, MD, Muenster, Germany (Abstract Co-Author) Nothing to DiscloseAnne Helfen, MD, Muenster, Germany (Abstract Co-Author) Nothing to DiscloseMiriam Stolting, Muenster, Germany (Abstract Co-Author) Nothing to Disclose

PURPOSE

Exosomes, small vesicles carrying inter alia proteins, miRNA and RNA, are important mediators in intercellular communication. Weassessed the in vivo biodistribution of exosomes from highly malignant breast cancer cells in comparison to exosomes from theserum of healthy mice, and their effect on the immune cell infiltrate in target organs of metastasis using molecular imaging.


Exosomes were isolated from the tissue culture supernatant of highly malignant 4T1 breast cancer cells or the serum of healthyBALB/c mice using a protocol comprising size-exclusion chromatography and ultracentrifugation. The purity of the isolate waschecked by electron microscopy and western blotting. After labeling with the fluorescent dye DiR (750/780 nm), exosomes wereinjected i.v. into healthy BALB/c mice and their distribution was assessed using fluorescence-reflectance imaging (FRI). After exvivo imaging of the organs, lungs and spleen were stained for FACS analysis of granulocytes, T- and B-cells to identify changes inthe immune cell content.

RESULTS

The assessment of the in vivo distribution of DiR-labeled exosomes with FRI showed exosomes from highly malignant 4T1 cells, incomparison to exosomes from the serum of healthy BALB/c mice, to preferentially accumulate in the target organs of metastasis, inthis case lung, liver and spine (tumor-exosomes vs. serum-exosomes: lung 18.6 vs. 10.4, p=0.01; liver 72.2 vs. 56.5, p=0.02; spine5.1 vs. 3.5, p<0.01). Furthermore, flow cytometry analysis of the immune cell composition revealed an increase of cytotoxic CD8+T-cells and a decrease of CD4+ T-helper cells in the lung. Also, we observed an increase in macrophages and a trend towards a

SSG07-06 Evaluation of the Efficacy of Superparamagnetic Iron Oxide-Labeled Bone Marrow Mesenchymal StemCells in the Treatment of Acute Myocardial Infarction in Rats by 7.0T MRI


SSG07-07 Construction of Pepstatin A-Conjugated Ultrasmall SPIONs for Targeted Positive MR Imaging ofEpilepsy-Overexpressed P-glycoprotein


decrease in monocytes.

CONCLUSION

Exosome accumulation changes the immune cell composition in target-organs of metastasis and can be visualized by FRI.


In vivo imaging allows to track labeled tumor-derived exosomes, providing information about their role in the metastatic spread ofsolid tumors.

ParticipantsXiaoxin Liu, Yinchuan, China (Presenter) Nothing to DiscloseYushu Chen, BSc, Chengdu, China (Abstract Co-Author) Nothing to DiscloseZiqian Xu, BSC, Chengdu, China (Abstract Co-Author) Nothing to DiscloseZhu Jing, Chengdu, China (Abstract Co-Author) Nothing to DiscloseXuejun Ping, Yinchuan, China (Abstract Co-Author) Nothing to DiscloseFabao Gao, MD, PhD, Chengdu, China (Abstract Co-Author) Nothing to Disclose


[email protected]

PURPOSE

To evaluated the efficacy of bone marrow mesenchymal stem cells (BMSCs) in the treatment of acute myocardial infarction (AMI) inrats by 7.0T MRI.


20 male SD rats were randomized into experiment group (n = 7) and normal control group (n = 7). Rats were anesthetized withchloral hydrate (0.3ml/100g). Opened the rats' chest and ligated the left anterior descending coronary artery to modeled AMI.25μg/ml Superparamagnetic Iron Oxide combined with 0.75μg/ml L-poly-lysine labeled BMSCs 48h, then BMSCs were collected anddirectly injected into the infarcted area. MRI scans were performed on D1 and D14 after modeling. Left ventricular ejection fraction(LVEF) and other cardiac function indexes, myocardial strain, the morphological changes of the infarcted area and the signal ofinfarcted area were used CVI42 software to analysis, then objectively evaluated the therapeutic effect of BMSCs on AMI.

RESULTS

The signal intensity of SPIO-labeled area in experimental group was significantly lower than control group and muscle (P<0.001).The values of end diastolic volume (EDV), end systolic volume (ESV), LVEF, peak strain radial (PSR) and peak strain circumferential(PSC) on D1 were 0.35 ± 0.12ml, 0.19 ± 0.09ml, 0.46 ± 0.08, 54.93 ± 15.83 and 24.50 ± 3.82 respectively in control group andwere 0.38 ± 0.13ml, 0.21 ± 0.06ml, 0.46 ± 0.05, 59.16 ± 12.23 and 26.24 ± 2.51 respectively in experiment group. Left ventricularwall thickness on D14 was significantly thinner than D1, and the values of EDV, ESV, LVEF, PSR and PSC on D14 became to 0.7 ±0.22ml, 0.46 ± 0.18ml, 0.35 ± 0.11, 38.84±15.84 and 20.24 ± 6.43 respectively in control group and were 0.54 ± 0.12ml, 0.33 ±0.07ml, 0.38 ± 0.05, 65.48 ± 14.35 and 27.21 ± 2.06 respectively in experiment group. The EDV, ESV and LVEF on the D1 and D14of the control group were no significantly different from the experimental group (P>0.05). There was no significant difference in PSRand PSC between the experimental group and the control group on D1 (P>0.05), but PSR and PSC on D14 of the control group weresignificantly lower than the experimental group (P<0.05).

CONCLUSION

BMSCs have no significantly improvement in EDV, ESV and LVEF in the treatment of AMI, but delay the myocardial strainimpairment. MRI can be used to evaluate the effect of SPIO-labeled BMSCs transplanted into AMI.


MRI can be used to evaluate the effect of SPIO-labeled BMSCs transplanted into AMI.

ParticipantsJun Zhang, MD, Shanghai, China (Presenter) Nothing to DiscloseChengjuan Du, Shanghai, China (Abstract Co-Author) Nothing to DiscloseDaoying Geng, Shanghai, China (Abstract Co-Author) Nothing to Disclose

PURPOSE

To develop the ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) for the highly sensitive T1-wighted MR imaging ofthe epileptogenic region by the positively enhanced T1 effect.


A peptide-targeted nanoprobe, based on ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs), PA-USPIONs, waselaborately constructed to enable highly selective delivery and sensitive T1-weighted positive magnetic resonance (MR) imaging ofthe epileptogenic region. Especially, Pepstatin A (PA), a small peptide which can specifically target to P-glycoprotein (P-gp)overexpressed at the epileptogenic region in a kainic acid (KA)-induced mice model of seizures, was conjugated onto the surface ofPEGylated USPIONs. The in vitro/vivo relaxivity of PA-USPIONs nanoprobes was conducted on a 3.0 T clinical MRI scanner at roomtemperature. Both of the in vitro/vivo biosafety evaluation of PA-USPIONs nanoprobes have been studied.

SSG07-08 Gene Reporter Technique Visualizing Cellular Gene Expression Based on MRI


SSG07-09 Multimodality Molecular Imaging of Lung Disease Using PET, CT and Optical Imaging

Tuesday, Dec. 3 11:50AM - 12:00PM Room: S505AB

RESULTS

The as-constructed PA-USPIONs nanoprobes have favorable T1 contrast enhancement and high r1 relaxivity compared with theclinically used T1-MR contrast agent (Gd-DTPA) by systematic in vitro and vivo assessments. Importantly, the toxicity evaluation,especially to brains, was assessed by the histological as well as hematological examinations, demonstrating that the fabricated PA-USPIONs nanoprobes are featured with excellent biocompatibility, guaranteeing the further potential clinical application.

CONCLUSION

In this work, a highly targeted positive MR contrast agent based on USPIONs by surface modification with PEG, followed byconjugation with Pepstatin A, PA-USPIONs, has been successfully constructed for sensitive and precise molecular T1-weighted MRimaging of the epileptogenic region that holds the high potential for precise resection of the according lesion in order to achievetherapeutic, often curative purposes.


N/A

ParticipantsHonsoul Kim, Seoul, Korea, Republic Of (Presenter) Nothing to DiscloseSong-Ee Baek, MD, Durham, NC (Abstract Co-Author) Nothing to Disclose


[email protected]

PURPOSE

The recent innovations in biology provides with new potential therapeutic strategies in medicine such as gene therapy and stem celltherapy. The purpose of this study was to develop a gene reporter technique for visualizing cellular gene expression using gadoxeticacid enhanced MRI.


We used a plasmid form human organic anion transporting protein (human OATP) 1B3 cDNA attached to CMV promoter (pCMV-hOATP1B3) to induce ectopic OATP expression in target cells. For comparison we used a blank plasmid with CMV promoter (pCMV-blank). HEK 293 cells (which are non-hepatocyte origin) were transfected with these DNAs. Western blot and confocal microscopyexam were performed to measure OATP protein expression. The cells were in vitro co-cultured at various concentrations ofgadoxetic acid for 24 hours. We made a cell phantom and obtained T1, T2 weighted images and performed T1 and T2 mapping with9.4T MRI. We also performed MRI of the xenograft tumor (pCMV-hOATP1B3 and pCMV-blank HEK 293) bearing nude mice before andafter intravenously injecting gadoxetic acid (1.2ul/g).

RESULTS

Western blot and confocal microscopy after OATP1B3 immunofluorescence staining revealed that pCMV-hOATP1B3 transfected HEK293 cells produced abundant OATP1B3 proteins which were localized on cell membrane. MRI of cell phantom showed that only thepCMV-OATP1B3 transfected cells could generate T1 contrast enhancement, which effect was strongest when the gadoxetic acidco-culture concentration was 1.2ul/ml. MRI of mice revealed that pCMV-OATP1B3 transfected HEK 293 xenografts but not pCMV-blank control xenografts showed contrast enhancement 15 minutes after gadoxetic acid enhancement which lasted up to 9 hours.

CONCLUSION

OATP1B3 gene can be genetically manipulated to induce OATP1B3 expression in target cells of non-hepatocyte origin and thatthese cells generate T1 contrast enhancement effect on gadoxetic acid enhanced MRI.


OATP1B3 gene can be used as a MRI gene expression reporter, which implies it can be applied for non-hepatocyte target cellselective imaging and context-dependent imaging.

ParticipantsAndrei Molotkov, MD,PhD, New York, NY (Abstract Co-Author) Nothing to DiscloseMonica P Goldklang, New York, NY (Abstract Co-Author) Nothing to DiscloseAdam Gerber, MD,PhD, New York, NY (Abstract Co-Author) Nothing to DiscloseTina Zelonina, New York, NY (Abstract Co-Author) Nothing to DiscloseJohn Castrillon, New York, NY (Abstract Co-Author) Nothing to DiscloseMikhail Doubrovin, MD, Memphis, TN (Abstract Co-Author) Spouse, Consultant, ATARA Biotherapeutics LtdJeanine M. D'Armiento, New York, NY (Abstract Co-Author) Nothing to DiscloseAkiva Mintz, MD, PhD, Paramus, NJ (Presenter) Consultant, Regeneron Pharmaceuticals, Inc

PURPOSE

Our long term goal is to develop novel therapies for lung diseases that involve pathologic permeability of the alveolar-capillarybarrier. Exposure to toxins, commonly used drugs and even surgical intervention have the potential of causing abnormal epithelialpermeability which is manifest as infiltrative processes on CT, including widespread infiltrates seen in acute respiratory distresssyndrome (ARDS). However, anatomic changes do not quantitate the underlying disease, which does not allow real-time diagnosisof subacute disease, response to therapy or personalization of treatment regiments. Therefore, our objective in this work is todevelop a translational quantifiable test of alveolar-capillary barrier integrity for the purpose of informing our drug discovery efforts.


We used a published model of ARDS, which involved intranasal delivery of LPS. 72 hours post LPS delivery, we intravenouslyinjected mice with Cy7- or 68-Gallium (68Ga) labeled mouse albumin. Two hours post tracer injection, we imaged mice using MILabsoptical imaging (OI)/CT platform and an Inveon PET scanner. Images were scanned on a common bed and automaticallycoregistered. Lung counts were obtained and quantified for both PET and optical imaging.

RESULTS

We observed significantly increased lung activity of Cy7-albumin on OI at 72 hours after LPS injection, which correlated with theabnormal appearance on gated microCT as well as quantification of the Cy7-albumin in the bronchoalveolar lavage (BAL) fluid. Inorder to translate these findings, we radiolabeled albumin with 68Ga, a short half-life positron emitting radioisotope that is used inclinical PET scans. We found that 72 hours after lung injury, [68Ga]albumin PET correlated with our optical imaging findings anddemonstrated abnormal activity in the lung fields, indicative of abnormal epithelial permeability.

CONCLUSION

[68Ga]albumin can be utilized as a translational radiotracer for quantifying the abnormal epithelial permeability that is the underlyingcause of various lung pathologies, including ARDS. Furthermore, the ability to use Cy7-albumin optical imaging as a preclinicaltranslational surrogate for [68Ga]albumin offers a high throughput means of rapidly screening potential therapeutics that aim toreverse the underlying disease process.


[68Ga]albumin PET/CT can potentially be utilized as a biomarker for various lung pathologies, including ARDS


MI208-SD-TUA1

Performance of 18F Cerenkov Luminescence Detection on General Optical Imaging Devices

Station #1

MI209-SD-TUA2

Simultaneously Calculation of Concentration of Contrast Media, Relaxivity, and Oxygen ExtractionFraction Using Quantitative Parameter Mapping

Station #2

MIS-TUA

Molecular Imaging Tuesday Poster Discussions

Tuesday, Dec. 3 12:15PM - 12:45PM Room: MI Community, Learning Center

MI



ParticipantsBenjamin Larimer, PhD, Charlestown, MA (Moderator) Co-founder, Cytosite Biopharma Inc; Consultant, Cytosite Biopharma Inc;Stockholder, Cytosite Biopharma Inc

Sub-Events

ParticipantsSuguru Katsube, Fukuoka, Japan (Presenter) Nothing to DiscloseMasayuki Sasaki, Fukuoka, Japan (Abstract Co-Author) Scholarship, Nihon Medi-Physics Co, LtdShingo Baba, Fukuoka, Japan (Abstract Co-Author) Nothing to DiscloseAkihiro Nohtomi, Fukuoka, Japan (Abstract Co-Author) Nothing to DiscloseToshioh Fujibuchi, Fukuoka, Japan (Abstract Co-Author) Nothing to DiscloseYuji Tsutsui, Fukuoka, Japan (Abstract Co-Author) Nothing to DiscloseNatsumi Shimokawa, Fukuoka, Japan (Abstract Co-Author) Nothing to DiscloseAya Takashima, Fukuoka, Japan (Abstract Co-Author) Nothing to DiscloseYuma Tsubaki, Fukuoka, Japan (Abstract Co-Author) Nothing to Disclose

PURPOSE

We aimed to examine the quantitative performance of general optical imaging devices for detecting Cerenkov luminescence.


STF-8300M (Santa Barbara Instrument Group) and PENTAX KP (RICOH Imaging Company) cameras were used for Cerenkovluminescence imaging. RIA tubes (6 mL) were filled with 18F solution of 0.01-340 MBq/mL and placed in a light-tight box. Dataacquisition was performed for 10, 30, 60, 180, and 360 seconds using the STF-8300M with binning 1 × 1, 15 × 15, and 30 × 30and lens to tube distance of 25 cm, while that using the PENTAX KP (ISO sensitivity 819200) was similar without binning. Theimages were acquired to evaluate the relationship between gray value and radioactivity concentration.

RESULTS

Minimum detectable radioactivity concentration was 0.22 MBq/mL with the STF-8300M (binning 15 × 15) and 13 MBq/mL with thePENTAX KP. A relationship between radioactivity and gray value was observed in both imaging devices. Gray value closelycorrelated with radioactivity with STF-8300M binning 1 × 1, 15 × 15 (R2 = 0.98) and PENTAX KP (R2 = 0.99) while it did not withSTF-8300M binning 30 × 30. Better quantification of performance was observed at the higher radioactivity concentration and whenusing longer acquisition times.

CONCLUSION

A linear relationship between radioactivity concentration and gray value was observed on general optical imaging devices, whilesensitivity of Cerenkov luminescence detection was not considered to be sufficient for clinical use.


Cerenkov luminescence imaging(CLI) is expected to make up the poor special resolution of PET and SPECT images. In addition,optical imaging devices are relatively inexpensive. CLI will be promising technique for detecting tumors.

ParticipantsYuki Matsumoto, MS, Tokushima, Japan (Presenter) Nothing to DiscloseMasafumi Harada, MD, PhD, Tokushima, Japan (Abstract Co-Author) Nothing to DiscloseYuki Kanazawa, PhD, Tokushima, Japan (Abstract Co-Author) Nothing to DiscloseTakashi Abe, MD, Tokushima, Japan (Abstract Co-Author) Nothing to DiscloseMaki Ohtomo, Tokushima-shi, Japan (Abstract Co-Author) Nothing to DiscloseYo Taniguchi, Kokubunji-shi, Tokyo , Japan (Abstract Co-Author) Employee, Hitachi, LtdMasaharu Ono, Tokyo, Japan (Abstract Co-Author) Employee, Hitachi, LtdYoshitaka Bito, PhD, Taito, Japan (Abstract Co-Author) Employee, Hitachi, Ltd


[email protected]

MI219-SD-TUA3

Facile Preparation of Near-Infrared Fluorescence and Magnetic Resonance Dual-Modality ImagingProbes Based on Mesoporous Organosilica Nanoparticles

Station #3

MI220-SD-TUA4

In Vivo Multimodal Imaging and Phototherapy of Triple-Negative Breast Cancer Using a Cathepsin B-Activated Probe

Station #4

PURPOSE

Our aim was to quantitatively map the concentration of contrast media (CM), relaxivity (r1), and oxygen extraction fraction (OEF)for detecting changes in tissue environment in brain diseases.


In this study, quantitative parameter mapping (QPM), which can simultaneously create quantitative maps of T1, T2, proton density(PD), and quantitative susceptibility mapping (QSM) of brain diseases treated with or without radiation therapy (n = 6), wasperformed on a 3T MRI system (Hitachi, Ltd.). R1 (reciprocal of T1 map) and QSM, before and after injection, were calculated (Gd-BTDO3A; Gadovist ®). CM map of Gd-BTDO3A and subtracted map of R1 (R1sub) were calculated from QSM and R1 map before andafter injection. Moreover, r1 of brain diseases was calculated from CM and R1sub (r1 = R1sub/CM). Additionally, OEF of areassurrounding the affected brain area was estimated using QSM before injection. After obtaining these quantitative maps, linear andnon-linear regression analyses were performed for CM, r1, and OEF. Finally, the statistical significance of differences in the patientswas calculated to compare whether changes in CM, r1, and OEF were dependent on brain diseases (P-value < 0.05).

RESULTS

The comparison between CM and R1sub maps of brain metastasis with radiotherapy is shown, demonstrating a strong correlation (R= 0.83). The non-linear regression analysis of r1 and OEF, including brain metastasis, with and without radiotherapy, showed goodcorrelation (R2 = 0.55). The differences in CM, r1, and OEF in patients who did and did not undergo radiotherapy were statisticallysignificant (P<0.001).

CONCLUSION

In conclusion, CM, r1, and OEF maps can measure changes in tissue environment in diseases.


Our methods may independently evaluate CM, r1, and OEF. Moreover, QPM can not only calculate CM, r1, and OEF but also cancalculate conventional weighed images such as T1w, T2w, T2* FLAIR before and after injection.

ParticipantsYanjiao Li, Shenzhen , China (Presenter) Nothing to DiscloseGuangyao Wu Sr, MD,PhD, Shenzhen, China (Abstract Co-Author) Nothing to DisclosePanying Wang, MD, Wuhan, China (Abstract Co-Author) Nothing to DiscloseXiangyu Wang, Shenzhen , China (Abstract Co-Author) Nothing to Disclose


[email protected]

PURPOSE

Facile prepared near-infrared fluorescence and magnetic resonance dual-modality imaging probes based on mesoporous organosilicananoparticles.


Firstly, mesoporous organosilica nanoparticle was prepared via a surfactantassembly sol-gel process in a Stöber solution. Then, thefunctional molecules with fluorescence and magnetic resonance effects are connected via click reaction.

RESULTS

Fourier transform infrared (FT-IR) spectra, zeta potentials, UV-vis spectra, and energy dispersive X-ray (EDX) spectrum confirm thesuccessful modifications of the functional molecules on the MONs. The prepared MON-Gd-Cy5.5-RGD probes shows excellent NIRFand MR imaging properties, and the relaxivity rate (r1) is measured up to 2.85 mM1 s 1. In addition, the MON-Gd-Cy5.5-RGD probesshow excellent in vitro and in vivo biocompatibility. Confocal laser scanning microscopy and flow cytometry reveal that theinternalization of MON-Gd-Cy5.5-RGD is significantly higher than the others. The ex vivo tumor NIRF images show strongerfluorescence intensity in the probe group, and the fluorescence intensity is significantly stronger. The tumor region exhibits astronger signal after injection of the probe in vivo MR imaging, and a relatively greater increase in brightness than the other groups.

CONCLUSION

In this work, near-infrared fluorescence (NIRF) and magnetic resonance (MR) dual-modality imaging probes are prepared onthioetherbridged mesoporous organosilica nanoparticles (MONs) via click reaction. It shows excellent in vitro and in vivobiocompatibility. Confocal laser scanning microscopy and flow cytometry demonstrate that the MON-GdCy5.5-RGD can efficientlytarget to MDA-MB-231 tumor cells. Additionally, ex vivo NIFR and in vivo MR imaging demonstrate that the MON-Gd-Cy5.5-RGDprobes can accumulate in tumor and improve the signals of tumor.


We rapid prepared a near-infrared fluorescence and magnetic resonance dual-modality imaging probe by using MONs which aremolecularly incorporated with thioether groups in the frameworks, bring unusual properties such as chemical stability, easilymodification via organic reaction, and excellent biocompatibility.

ParticipantsYanshu Wang, Shanghai, China (Presenter) Nothing to DiscloseDefan Yao, Shanghai, China (Abstract Co-Author) Nothing to Disclose

MI006-EB-TUA

Next Generation Sequencing for the Practicing Radiologist

Hardcopy Backboard

Dengbin Wang, MD, Shanghai, China (Abstract Co-Author) Nothing to Disclose

PURPOSE

Triple-negative breast cancer (TNBC) is considered incurable with currently available treatments. In light of upregulated cathepsin-B (CTSB) in TNBC, a targeted near-infrared activatable MRI/fluorescent /photoacoustic (MRI/NIR FL/PA) probe (Pep-SQ@USPIO) issynthesized for the selective detection of TNBC-derived CTSB and followed with photothermal/photodynamic therapy (PTT/PDT).


Pep-SQ@USPIO based on USPIO core modified with Pep-SQ. The sequence of Pep-SQ consisted of two moieties: the first moiety isTNBC targeted peptide (Pep) which labelled with a green fluorescent group, naphthalimide; the sencond moiety is an NIRfluorescent dye (SQ), of which it's essential properties of NIR FL/PA imaging and PTT/PDT. The two moieties linked via a CTSB-activated peptide. Transmission electron microscopy images, hydrodynamic size profiles, and absorption spectra of Pep-SQ@USPIOwere acquired before and after addition of CTSB at different periods of time. After incubation with probe, MDA-MB-231 and MCF-7cells fluorescence images were obtained with a confocal microscope. Test Pep-SQ@USPIO toxicity with or without laser irradiationby CCK-8 assay and singlet oxygen generation. The in vivo imaging application and antitumor efficacy are evaluate by injectingPep-SQ@USPIO into tumor bearing mice.

RESULTS

T1 and T2 relaxivity values of Pep-SQ@USPIO were measured to be 9.49 and 39.11 mM-1.s-1, respectively. Pep-SQ@USPIO itselfcan produce ROS as a PDT agent. After undergoing CTSB-triggered degradation, the activated probes recover the quenched NIR FLsignal with response, and their self-assemble in situ significantly enhances PTT efficacy. Pep-SQ@USPIO against the CTSB-highMDA-MB-231 cells with a lower IC50 compared to CTSB-low MCF-7 cells (p<0.05). Pep-SQ@USPIO was also successfully applied tothe in vivo imaging and phototherapy of tumors.

CONCLUSION

Pep-SQ@USPIO can act as MRI and PDT agent. Triggered by CTSB, the probe can recover the quenched NIR FL signal and providean enhanced photothermal conversion behavior, which enables NIR FL/PA imaging of CTSB activtity and aggregation enhanced PTTof TNBC.


This tumor-specific theranostic probes can precisely diagnose and exerts further selective treatment, which may addresschallenges faced by traditional medicine of TNBC.

ParticipantsVidur Mahajan, MBBS, New Delhi, India (Presenter) Researcher, CARING; Associate Director, Mahajan Imaging; Researchcollaboration, General Electric Company ; Research collaboration, Koninklijke Philips NV; Research collaboration, Qure.ai; Researchcollaboration, Predible Health; Research collaboration, Oxipit.ai; Research collaboration, Synapsica; Research collaboration, QuibimShelly Mahajan, New Delhi, India (Abstract Co-Author) Nothing to DiscloseHarsh Mahajan, MD,MBBS, New Delhi, India (Abstract Co-Author) Director, Mahajan Imaging Pvt Ltd; Research collaboration, GeneralElectric Company; Research collaboration, Koninklijke Philips NV; Research collaboration, Qure.ai; Research collaboration, PredibleHealth


[email protected]

TEACHING POINTS

Next Generation Sequencing (NGS) is a technique of reading the entire genome or screening few relevant genes for aberrations.NGS sequences DNA parallelly thus resulting in reduced price and high speed of genome sequencing. For Onco-Radiologists: NGS,can detect inherited or sporadic germline mutations or acquired changes i.e. somatic mutations on tumour tissues. Identification ofgermline mutations helps in confirming the diagnosis, better management of diseases, prognosis and suggest preventive andsurveillance measures for at risk unaffected relatives. Few radiological outcomes are spot diagnosis for a few cancer geneticssyndrome. Somatic analysis of tumour biopsy helps in predicting the response of targeted therapy, prognostication andpharmacogenomics. For Ultrasonologists - For prenatal cases with abnormal USG findings, Non - Invasive Prenatal Techniques(NIPT), is a test that detects small amounts of cell free fetal DNA in the maternal bloodstream, allowing prenatal genetic diagnosisthrough maternal blood.


What is next generation sequencing? Germline vs somatic mutation detection Germline - applications in clinical care Somaticmutations - large gene panels - what is their use? NIPT - how can radiologists use it Imaging + genomics - the future?


MI210-SD-TUB1

CT-Based Radiomic Features as Prognostic Factors in ALK-Positive Non-Small-Cell Lung Cancer

Station #1

MI221-SD-TUB2

The Use of Near Infrared Radiation Spectroscopy (NIRS) in Reconstructing 3D Oxygenated DynamicImages as Biomedical Evidence in Monitoring Diabetic Foot

Station #2

MIS-TUB

Molecular Imaging Tuesday Poster Discussions

Tuesday, Dec. 3 12:45PM - 1:15PM Room: MI Community, Learning Center

CH MI


ParticipantsBenjamin Larimer, PhD, Charlestown, MA (Moderator) Co-founder, Cytosite Biopharma Inc; Consultant, Cytosite Biopharma Inc;Stockholder, Cytosite Biopharma Inc

Sub-Events

ParticipantsHailin Li, Beijing, China (Presenter) Nothing to DiscloseJingyun Shi, Shanghai, China (Abstract Co-Author) Nothing to DiscloseDi Dong, PhD, Beijing, China (Abstract Co-Author) Nothing to DiscloseJie Tian, Beijing, China (Abstract Co-Author) Nothing to Disclose


[email protected]

PURPOSE

To describe progression-free survival (PFS)-related radiomic features, and build a computed tomography (CT)-based radiomicsignature for the prediction of PFS in stage IV anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC)patients treated with tyrosine kinase inhibitor (TKI) crizotinib.


From January 2012 to September 2016, 85 patients with ALK-mutant NSCLC who received crizotinib therapy were contained in thisstudy, which was examined and approved by the review committee as a retrospective research. We extracted 481 quantitative 3Dfeatures including intensity, texture, and wavelet features of NSCLC tumor images from the manually segmented tumor volumes ofinterest. The prognostic performance of each radiomic feature was assessed by hazard ratio (HR) in the whole cohort. Then, allpatients were randomly divided into a training cohort (n=43) and an independent validation cohort (n=42). In the training cohort, aCT-based radiomic signature was built for PFS prediction using a Cox proportional hazards model with the least absolute shrinkageand selection operator penalty. The performance of the radiomic signature was evaluated in the validation cohort using the Kaplan-Meier survival analysis and Harrell's concordance index (C-index).

RESULTS

After calculating the HR of all radiomic features, 22 radiomic features with P values less than 0.05 were screened out, and 68% ofthem were grey-level co-occurrence matrix (GLCM) texture features. A radiomic signature containing 2 CT-based radiomic features(both GLCM texture features) showed significant prognostic performance in the validation cohort (C-index, 0.654; 95% confidenceinterval, 0.556-0.753). A significant association between the radiomic signature and PFS was demonstrated in view of the Kaplan-Meier method and log-rank test (P < 0.01) in statistical analysis.A significant association between the radiomic signature and PFSwas demonstrated in view of the Kaplan-Meier method and log-rank test (P < 0.01) in statistical analysis.

CONCLUSION

In ALK mutated NSCLC patients, the GLCM texture features showed good prognostic performance, the CT-based radiomic modelwas found to be effective for predicting PFS.


This study discussed the correlation of a radiomic signature with progression-free survival and its predictive potential in stage IVALK-positive NSCLC patients treated with crizotinib. The radiomic signature was found can predict resistance to ALK inhibitor, whichcan improve the individualized treatment with ALK inhibitors.

ParticipantsMezie Laurence B. Ortiz, BSC,MA, Busan, Korea, Republic Of (Presenter) Nothing to DiscloseAxel Yen C. Garcia, BSC,RT, Sasang-gu , Korea, Republic Of (Abstract Co-Author) Nothing to DiscloseYoung-Jin Jung, PhD, Busan, Korea, Republic Of (Abstract Co-Author) Nothing to Disclose

PURPOSE

This study aims to provide biomedical images as clinical evidence using Near Infrared Radiation in monitoring diabetic foot whichcould be of use in improving patient's quality of life for it is portable, non-invasive, non-ionizing and not requiring manual calibration,

MI222-SD-TUB3

The Value of Multifunctional Caramelized Fe3O4 Nanospheres in Magnetic Resonance Imaging, MRI,and Photothermal Therapy for Breast Cancer

Station #3

additional medical supplies, and specifically trained personnel.


The Toast C++ and MATLAB 2018b software applications were used to reconstruct 3D mesh files of the skin and bones of the foot.Subsequently, Diffuse Optical Tomography (DOT) method was applied to the generated mesh files having the forward and inverseproblem for image reconstruction. In forward problem, diffusion equation was applied to predict the emission of NIR light based onthe light source and interacting material parameters. Meanwhile, the inverse problem applied the forward problem to reconstruct theoptical property distribution of interacting material from a measured data set.

RESULTS

The hemoglobin concentration measured allowed the 3D reconstruction of oxygenated dynamic imaging, in particular, the absorptionreconstruction. The result illustrates the differences in the diffusive regime imaging of bodily structures and among the fourreconstructions, absorption recon 1 has the lowest color map value ranging from 0.100000005 to 0.100000015 and absorptionrecon 11 have the highest color map values obtained ranging from 0.0105 to 0.0115. Absorption recon 1 has the lowest range ofcolor map values for diffuse optical tomography occur in the most deep-seated area in comparison with the other three absorptionreconstructions. On the other hand, absorption recon 11 is in the most superficial area.

CONCLUSION

Contact and Remote based Near Infrared Spectroscopy could be of use in monitoring diabetic foot and the reconstructed 3Doxygenated dynamic images could be of use as biomedical evidence.


NIR specifically works by exploring the oxygenated and deoxygenated hemoglobin concentration in the body which paved the wayfor the measurement of hemoglobin concentration that is used to identify wound healing potential.

ParticipantsFang-qing Wang, Jinan , China (Presenter) Nothing to DiscloseDe-xin Yu, Jinan , China (Abstract Co-Author) Nothing to DiscloseHong Wang Jr, Jinan, China (Abstract Co-Author) Nothing to Disclose

PURPOSE

To investigate the diagnostic and therapeutic effect of multifunctional caramelized Fe3O4 (Fe3O4-CNSs) in MRI and photothermaltherapy for breast cancer.


Fe3O4 and DOX were integrated into caramel carbon nanospheres (CNSs) by covalent binding and electrostatic adsorption , thentheir physical and chemical characteristics and cytotoxicity were determined. The subcutaneous xenograft of 4T1 cells in BALB-Cmice was established. The mice models were divided into three groups, and then the saline (control group), Fe3O4@CNSs andFe3O4@CNSs+DOX were injected through the mice tail vein respectively. After MR imaging at different time points (0, 3, 12, 24, 48and 72 h), the changes in T2 signal value of the tumor were measured. At the time point of the peak value, the laser irradiationwas performed for 10 minutes for photothermal therapy, and then irradiated again after 3 and 6 days, and the temperature changeswere recorded. The imaging and therapeutic results were compared with the changes of tumor volume and the pathologicalfindings.

RESULTS

Fe3O4@CNSs were cultured in MCF-10A cells at 200 ppm for 48 hours, and the cell viability was 82%. In Fe3O4@CNS orFe3O4@CNSs@DOX group, the T2 signal value of tumor was gradually decreased within 24 hours, and reached the peak lowestvalue at 24 hour.Accumulation of Fe3O4@CNSs or Fe3O4@CNSs@DOX in the tumor resulted in increased temperature to 62 ? forphotothermal therapy, 25 ? higher than that of the control group. Tumor volume ratio in Fe3O4@CNSs@DOX group was 0.8 in thetwelfth day and the necrosis was more than that in control group or in Fe3O4@CNSs group.

CONCLUSION

Fe3O4@CNSs with higher biocompatible and self-degradable characteristics can realize the integration of MRI and photothermaltherapy simultaneously, which is of great help to the diagnosis and treatment for breast cancer.


Fe3O4-CNSs with MRI imaging and photothermal therapy functions provide a novel method for the precise and comprehensivediagnosis and treatment of breast cancer.


SSJ14-01 To Evaluate the Efficacy of 68Ga-DOTA-TOC and 18F-FDG PET/CT in the Follow-Up of Patients withNeuroendocrine Tumor Treated with the First Full Peptide Receptor Radionuclide Therapy Cycle

Tuesday, Dec. 3 3:00PM - 3:10PM Room: S504CD

SSJ14-02 Inlaying Radiosensitizer onto the Polypeptide Shell of Drug-Loaded Ferritin for Imaging andCombinational Chemo-Radiotherapy


SSJ14

Molecular Imaging (Theranostics)


MI

AMA PRA Category 1 Credit ™: 1.00ARRT Category A+ Credit: 1.00


ParticipantsChristopher C. Riedl, MD, New York, NY (Moderator) Nothing to DiscloseGabriel C. Fine, MD, Salt Lake City, UT (Moderator) Nothing to Disclose

Sub-Events

ParticipantsSikandar M. Shaikh, DMRD, Hyderabad, India (Presenter) Nothing to Disclose


[email protected]

PURPOSE

To evaluate the value of 68Ga-DOTA-TOC and 18F-FDG PET/CT for initial and follow-up evaluation of patients with neuroendocrinetumour (NET) treated with peptide receptor radionuclide therapy (PRRT).


We evaluated 33 patients who were histologically proven NET.All these patients underwent both PRRT and three combined 68Ga-DOTA-TOC and 18F-FDG PET/CT studies. 68Ga-DOTA-TOC PET/CT was performed before PRRT, 3 months after completion of PRRTand after a further 6 - 9 months. 18F-FDG PET/CT was done within 2 months of 68Ga-DOTA-TOC PET/CT. Follow-up ranged from11.8 to 80.0 months (mean 34.5 months).

RESULTS

All patients were 68Ga-DOTA-TOC PET-positive initially and at follow-up after the first full PRRT cycle. Overallx31 of the 99 18F-FDG PET studies (31 %) were true-positive in 19 of the 33 patients (58 %). Of the 33 patients, 14 (3 grade 1, 11 grade 2) were18F-FDG-negative initially and during follow-up (group 1), 12 (3 grade 1, 6grade 2, 3 grade 3) were 18F-FDG-positive initially andduring follow-up (group 2), 5 patients (1 grade 1, 3 grade 2, 1 grade 3) were 18F-FDG-negative initially but 18F-FDG-positiveduring follow-up (group 3), and 3 patients (all grade 2) were 18F-FDG-positive initially but 18F-FDG-negative during follow-up(group 4).18F-FDG PET showed more and/or larger metastases than 68Ga-DOTA-TOC PET in three patients of group 2 and twopatients of group 3, all with progressive disease. In two patients with progressive disease who died during follow-up tumourSUVmax increased by 41 - 82 % from the first to the last follow-up investigation.

CONCLUSION

In known NET patients, the presence of 18F-FDG-positive tumours correlates strongly with a higher risk of progression. Initially,patients with 18F-FDG-negative NET may show 18F-FDG-positive tumours during follow-up. Also patients with grade 1 and grade 2NET may have 18F-FDG-positive tumours. Therefore, 18F-FDG PET/CT is a complementary tool to 68Ga-DOTA-TOC PET/CT withclinical relevance for molecular investigation.


Thus FDG PET-CT and Thus FDG PET-CT and 68Ga-DOTA-TOC PET-CT are complimentary to each other in evalaution and follow upafter theraphy.

ParticipantsJingwen Chen, Shanghai, China (Presenter) Nothing to DiscloseQiuhong Zhang, Shanghai, China (Abstract Co-Author) Nothing to DiscloseHan Wang, MD, PhD, Shanghai, China (Abstract Co-Author) Nothing to Disclose

PURPOSE

Ferritin with unique hollow cavity is an emerging protein-based nanoplatform for anticancer-drug delivery, but the in vivo

SSJ14-04 A Fibronectin-Targeting Dual-Modal NIR-II Fluorescent and Photoacoustic Nanodots for BreastCancer Imaging and Phototherapy


SSJ14-05 Radiosynthesis and Initial Evaluation of [11C]AG-488: Novel Dual-Targeted Anti-GBM Agent


chemotherapeutic effectiveness is still unsatisfactory with such a monotherapy modality, which is urgently in need of improvement.


Here a novel ferritin nanotheranostic with anticancer-drug doxorubicin encapsulated into its hollow interior and nanoradiosensitizerbismuth sulfide nanocrystals inlayed onto its polypeptide shell was synthesized for combinational therapeutic benefits. Theformation mechanism of bismuth sulfide nanocrystals based on ferritin has been analyzed. The in vitro and in vivo treatment effectswere carried out on HeLa cancer cells and tumor-bearing mice, respectively. The biocompatibility and excretion of the ferritinnanotheranostic have also been evaluated to guarantee their biosafety.

RESULTS

The polypeptide shell of ferritin provides nucleation sites for the bismuth sulfide nanocrystals through coordination interaction, andsimultaneously inhibits the further growth of bismuth sulfide nanocrystals, rendering the bismuth sulfide nanocrystals like rivetsinlaying onto the polypeptide firmly, which can not only strengthen the architectural stability of ferritin to prevent drug burstleakage during systemic circulation, but also act as excellent computed tomography contrast agents and nanoradiosensitizers for invivo imaging-guided cancer combinational treatments.

CONCLUSION

The design concept of inlaying bismuth sulfide nanocrystals onto the polypeptide shell of doxorubicin-encapsulated ferritinsignificantly inhibits the tumor growth and simultaneously further broadens the application of ferritin in nanomedicine.


The Bi2S3 nanocrystals onto the polypeptide shell can act as contrast agents for CT imaging, which can indicate the efficienttumor accumulation of Dox@AFBS through EPR effect after systemic administration, offering imaging guidance for in vivo cancertreatment.

ParticipantsDefan Yao, Shanghai, China (Presenter) Nothing to DiscloseYanshu Wang, Shanghai, China (Abstract Co-Author) Nothing to DiscloseDengbin Wang, MD, Shanghai, China (Abstract Co-Author) Nothing to Disclose

PURPOSE

Metastasis is the primary cause of death in breast cancer patients. Early diagnosis of high-risk breast cancer, including metastasis,requires accurate imaging of tumor biomarker for tailoring appropriate interventional therapies. Increased fibronectin expression, ahallmark of epithelial-tomesenchymal transition, is associated with high-risk breast cancer and metastasis. A fibronectin-targetingdual-modal NIR-II fluorescent and photoacoustic nanoprobe is synthesised for breast cancer imaging andphotothermal/photodynamic therapy (PTT/PDT).


Organic NIR-II fluorescent squaraine dyes were achieved through an organic synthetic reaction. Encapsulation of the dyes in apolymer matrix yields nanodots showing a large absorptivity at 915 nm and an emission maximum near 1000 nm. Further decorationof the nanodots with a penta-peptide CREKA (Cys-Arg-Glu-Lys-Ala) yields targeted nanodots, SQ@DSPE, which binds to fibronectinthat are abundant in the tumour microenvironment of fast-growing breast cancer.

RESULTS

The nanodots SQ@DSPE showed a large absorptivity at 915 nm and an emission maximum near 1000 nm. The large NIR absorptivityof the nanodots facilitates NIR-I photoacoustic imaging and NIR-II fluorescence imaging. We find that the targeted nanodots couldbe used as deep intravascular contrast and provides robust signal enhancement in high-risk breast cancer, including metastasis.The photothermal conversion behavior and photodynamic activity of the nanodots enables PTT/PDT of breast cancer.

CONCLUSION

We report the NIR-II fluorescent molecule for dual fluorescence and photoacoustic imaging. The formulated nanodots have beensuccessfully used for dual NIR-II fluorescence and NIR-I photoacoustic imaging for precise noninvasive angiography. The synergeticbimodal imaging with targeting CREKA-decorated nanodots showed precise breast cancer-tumor diagnosis with good specificity andhigh sensitivity. Collectively, the bright nanodots hold great promise for monitoring and visualizing vascular and breast tissueabnormalities.


This research demonstrates the promise of NIR-II molecules and nanodots in dual-modal NIR-II fluorescence and NIR-Iphotoacoustic imaging for early detection of high-risk breast cancer and metastasis.

ParticipantsPatrick Carberry, PhD, New York, NY (Abstract Co-Author) Nothing to DiscloseAndrei Molotkov, MD,PhD, New York, NY (Abstract Co-Author) Nothing to DiscloseJongho Kim, MD, PhD, Tenafly, NJ (Abstract Co-Author) Nothing to DiscloseMikhail Doubrovin, MD, Memphis, TN (Abstract Co-Author) Spouse, Consultant, ATARA Biotherapeutics LtdJaya Prabhakaran, PhD, New York, NY (Abstract Co-Author) Nothing to DiscloseJohn Castrillon, New York, NY (Abstract Co-Author) Nothing to DiscloseJ. John Mann, MD, New York, NY (Abstract Co-Author) Nothing to Disclose

SSJ14-06 First-In-Human Imaging of 89Zr-Daratumumab for CD38 Targeted Imaging of Myeloma


Dileep Kumar, PhD, New York, NY (Abstract Co-Author) Nothing to DiscloseAkiva Mintz, MD, PhD, Paramus, NJ (Presenter) Consultant, Regeneron Pharmaceuticals, Inc

PURPOSE

PET imaging plays a critical role in the diagnosis of disease. Our goal is to extend its use into the drug development arena byradiolabeling experimental therapeutics and studying their biodistribution in hard to reach malignancies like brain cancer.Glioblastoma (GBM) is malignant Grade IV brain cancer that is invariably fatal with a median survival of about 14 months.Chemotherapy and novel molecular strategies often fail due to the inability of drugs to pass through the BBB. Thus, PET offers areal-time tool to evaluate drug kinetics and tumor access. AG-488 (FLAG-003) is a novel ligand with established anti-angiogeneticand anti-microtubule properties in tumor cells and murine models of cancer. In preclinical models of GBM, AG-488 has been shown toreduce tumor volume and prolong survival and is in early stage clinical trials. The goal of this work is to radiolabel AG-488 with thepositron emitter 11C and demonstrate BBB permeability of this novel drug.


The radiochemical synthesis of [11C]AG-488 was optimized reacting [11C]CH3I in a GE FxMeI module. MicroPET/CT were obtaineddynamically for 60 minutes following IV injection of 50-100µl of [11C]AG-488. Image analysis was performed on PMOD software.

RESULTS

[11C]AG-488 was obtained in high radiochemical purity (>98%) and specific activity (2.5+/-0.5 Ci/mmol) in 30+/-5% radiochemicalyield, decay corrected to EOS. MicroPET imaging revealed distribution in the heart, lungs and liver as well as good BBB penetration,manifested by increased initial tracer uptake and significant retention in the brain over time, similar to what is seen in our previouswork with microtubule-specific tracers.

CONCLUSION

[11C]AG-488 can be synthesized with a high purity and yield and significantly crosses the BBB. We anticipate using [11C]AG-488 tohelp expedite the development of this novel dual-target drug as well as a potential companion diagnostic. We are therefore planningon further studying [11C]AG-488 in various orthotopic GBM models.


AG-488 is a novel dual action drug that is being tested on high grade glioma, a devestating disease. We succesfully synthesized[11C]AG-488 to demonstrate blood brain barrier penetration on PET imaging and are studying its use to diagnose and stratify GBMpatients.

ParticipantsGary A. Ulaner, MD,PhD, New York, NY (Presenter) Research support, General Electric Company; Research support, F. Hoffmann-LaRoche Ltd; Research support, Novartis AG; Research support and Consultant, sanofi-aventis Group; Research support, sanofi-aventis GroupNicholas Sobol, New York , NY (Abstract Co-Author) Nothing to DiscloseJoe O'Donoghue, New York, NY (Abstract Co-Author) Nothing to DiscloseSerge Lyashchenko, New York, NY (Abstract Co-Author) Nothing to DiscloseJason S. Lewis, PhD, New York, NY (Abstract Co-Author) Shareholder, Koninklijke Philips NV; Research support, MabVaxTherapeutics, Inc; Research support, Eli Lilly and Company; Research support, Sapience Therapeutics, Inc; Research support,SibTech, Inc; Research support, ImaginAb, Inc; Advisory Board, Telix Pharmaceuticals Ltd ; Advisory Board, Fuzionaire, Inc;Advisory Board, Trace-Ability, Inc; Stock, Telix Pharmaceuticals Ltd ; Stock, Fuzionaire, Inc; Stock, Trace-Ability, Inc; AdvisoryBoardl, Clarity Pharmaceuticals; Advisory Board, Varian Medical Systems, Inc; C Ola Landgren, New York , NY (Abstract Co-Author) Nothing to Disclose


[email protected]

PURPOSE

CD38 is an established therapeutic target in multiple myeloma that is expressed at high density by almost all myeloma cells.Daratumumab is an FDA-approved therapeutic antibody that binds directly to CD38. Our objective was first-in-huma imaging with89Zr-radiolabeled daratumumab for CD38-targeted imaging of myeloma.


Ten myeloma patients received 2 mCi of intravenous 89Zr-DFO-daratumumab in 20 or 50 mg of total antibody mass. Each patientunderwent 4 PET/CT scans over the next 8 days, as well as blood draws and whole-body counts, to determine tracerbiodistribution, pharmacokinetics, and radiation dosimetry.

RESULTS

Phase I first-in-human 89Zr-DFO-daratumumab PET/CT imaging demonstrated distribution in the blood pool, liver and spleen. A totalantibody mass of 20 or 50 mg provided successful immunoPET imaging, while 3 mg total antibody mass demonstrated excessivebackground accumulation of tracer in the bone marrow, liver, and spleen. Imaging on days 5-8 provided superior tumor-to-background ratios than on days 1-4. Focal 89Zr-DFO-daratumumab uptake was visualized in previously known as well as unknownsites of osseous myeloma, consistent with successful CD38-targeted immunoPET imaging of myeloma in human patients.

CONCLUSION

89Zr-DFO-daratumumab provides successful whole-body PET visualization of myeloma in a first-in-human phase I trial of myelomapatients.


This novel PET antibody will be tested for its potential to provide sensitive detection of myeloma, determine minimal residual disease

This novel PET antibody will be tested for its potential to provide sensitive detection of myeloma, determine minimal residual disease(MRD) status after completion of therapy, predict the effectiveness of daratumumab therapy, and serve as the basis of theranosticconstructs for patients with myeloma.


ED015-WE

Molecular Imaging Wednesday Case of the Day

Wednesday, Dec. 4 7:00AM - 11:59PM Room: Case of Day, Learning Center



TEACHING POINTS



SSK13-01 To Examine the Potential Role of 2-fluorodeoxyglucose Positron Emission Tomography Integratedwith CT (FDG-PET/CT) in Monitoring IFIs and Therapy Decision-Making

Wednesday, Dec. 4 10:30AM - 10:40AM Room: S505AB

SSK13-02 Glycosaminoglycan Chemical Exchange Saturation Transfer Imaging of the Talocrural Joint in Patientswith Osteochondral Lesions and Healthy Volunteers


SSK13

Molecular Imaging (General Subspecialties)

Wednesday, Dec. 4 10:30AM - 12:00PM Room: S505AB

MI



ParticipantsKathryn A. Morton, MD, Salt Lake City, UT (Moderator) Nothing to Disclose

Sub-Events

ParticipantsSikandar M. Shaikh, DMRD, Hyderabad, India (Presenter) Nothing to Disclose

PURPOSE

Invasive fungal infections (IFIs) are most common in immunosuppressed patients and can be life-threatening. Inadequate or notreatment is associated with high morbidity and mortality. We examined the potential role of 2-fluorodeoxyglucose positron emissiontomography integrated with CT (FDG-PET/CT) in monitoring IFIs and therapy decision-making.We also evaluated the role of baselinemetabolic parameters in predicting the metabolic response.


All patients between April 2016 and March 2019 who were diagnosed with IFIs, and underwent treatment with antifungal drugs, andwho also underwent FDG-PET/CT at baseline and at one or more timepoints during treatment were retrospectively included. Thepatient data was reviwed for pathology, microbiology, and laboratory findings. All FDG-PET/CT scans were performed according tostandardized protocols. For each scan, the global total lesion glycolysis (TLG) and metabolic volume (MV), highest maximumstandardized uptake value (SUVmax), and peak standardized uptake value (SUVpeak) were determined. The role of FDG-PET/CT onmonitoring antifungal therapy was assessed by looking at the clinical decision made as result of the scan. Furthermore, the addedvalue of the baseline metabolic parameters in predicting metabolic response to the antifungal treatment was evaluated.

RESULTS

Twenty-eight patients who underwent total 98 FDG-PET/CT scans were included with a mean age of 43?±?22 years. FDG-PET/CTresults altered management in 14 out of the 28 patients (50%). At the final FDG-PET/CT scan, 19 (68%) had a complete metabolicresponse (CMR), seven a partial response and two patients were defined as having progressive disease. Using receiver operativeanalysis, the cut-off value, sensitivity, specificity, and significance for the baseline TLG and MV to discriminate patients with CMRwere 160, 94%, 100%, p? CONCLUSION

FDG-PET/CT is useful in the monitoring of IFIs resulting in management therapy change in half of the patients. Baseline TLG and MVwere found to be able to predict the metabolic response to antifungal treatment.


FDG PET-CT has potential role in the evalaution of Fungal Infections and impact on treatment.

ParticipantsDaniel B. Abrar, MD, Dusseldorf, Germany (Presenter) Nothing to DiscloseMiriam Frenken, Dusseldorf, Germany (Abstract Co-Author) Nothing to DiscloseAnja Lutz, Dusseldorf, Germany (Abstract Co-Author) Nothing to DiscloseLaszlo Kasprowski, Dusseldorf, Germany (Abstract Co-Author) Nothing to DiscloseMatthias Boschheidgen, Dusseldorf, Germany (Abstract Co-Author) Nothing to DiscloseGerald Antoch, MD, Dusseldorf, Germany (Abstract Co-Author) Nothing to DiscloseChristoph Schleich, MD, Dusseldorf, Germany (Abstract Co-Author) Nothing to Disclose

PURPOSE

To optimize a glycosaminoglycan chemical exchange saturation transfer (gagCEST) protocol for imaging of glycosaminoglycans(GAG) at 3T and to compare gagCEST values between patients with osteochondral lesions and healthy volunteers (HV).


We used Bloch-McConnel simulations for optimization of the gagCEST protocol. Therefore, the following T1 and T2 relaxation times

SSK13-03 Insect Larvae in Medical Imaging: New Screening System for Gut Inflammatory Compounds UsingCT, MR, and PET


SSK13-04 Pharmacological Activation of Human Brown Adipose Tissue is Less Effective than Cold Exposure


We used Bloch-McConnel simulations for optimization of the gagCEST protocol. Therefore, the following T1 and T2 relaxation timesof cartilage at 3T were used: T1 = 1.2 s, T2 = 0.039 s.11 HV (age 24 ± 5 years) and 4 patients (age 32 ± 9 years) withostheochondral lesions were examined with the optimized gagCEST protocol. In addition, T1 and T2 values were determined toevaluate, if the relaxation times used in the simulation were accurate. Sequence parameters of the gagCEST sequence were: FOV= 160 x 160 mm², slice thickness = 5 mm, TE/TR = 3.5ms/7.2ms. 25 CEST images with a frequency offset between -3 ppm and 3ppm and one S0 image were recorded. An acquisition of an additional water saturation shift referencing sequence was applied inorder to correct remaining magnetic field inhomogeneities.

RESULTS

The optimization with the Bloch-McConnel simulations showed an ideal B1 amplitude of 0.8 µT and a pulse and interpulse duration of300 ms. We found a mean T1 time of (0.88 ± 0.13) s and a mean T2 time of (0.033 ± 0.005) s. These values significantly differedfrom values used in simulation. Nevertheless, further simulations revealed the same optimal pulse sequence parameters for the CESTsequence. HVs showed a significant higher gagCEST effect compared to patients (HV: MTRasym = (1.40 ± 0.71) %; patients:MTRasym = (0.05 ± 0.28) %; p-value < 0.01).

CONCLUSION

The proposed gagCEST protocol showed good performance and could distinguish between HV and patients with ostheochondrallesions.


Our proposed gagCEST protocol allows for further molecular investigation of cartilage at the talocrural joint in different clinicalsettings and larger studies.

ParticipantsAnton G. Muller, MSc, Heuchelheim, Germany (Presenter) Nothing to DiscloseFrank Hugo Heinz Muller, MD, Neustadt Weinstrase, Germany (Abstract Co-Author) Investigator, General Electric CompanyMichael Hentschel, PhD, Bern, Switzerland (Abstract Co-Author) Nothing to DiscloseMarian Kampschulte, MD, Giessen, Germany (Abstract Co-Author) Nothing to DiscloseFlorian H. Leinberger, Giesen, Germany (Abstract Co-Author) Nothing to DiscloseTine E. Trenczek, PhD, Giessen, Germany (Abstract Co-Author) Nothing to Disclose


[email protected]

PURPOSE

This study aims to propose and validate CT, MR and PET imaging features of gut inflammation in the insect Manduca sexta. TheEpithelial structure and intestinal innate immune response in M.sexta are functionally and mechanistically comparable to humans,making M.sexta a valuable model to study the innate part of gut inflammation. This, together with the cost-effective raring and thelarge, cylindrical gut of M.sexta larvae will provide a quick and easy system to screen for new effectors and inhibitors of gutinflammation for pharmaceutical purposes.


We established contrast-enhanced CT and MR as well as FDG-PET imaging, methods firstly applied to insects, to detect gutinflammation. Bacillus thuringiensis infected animals(n=19) were used as a positive control and compared to healthy animals(n=20).The gut wall of Bt and control animals were analyzed for histopathologic evidence of inflammation via cryosections. Then, ROCcurves of contrast-enhanced MR and CT gut wall thickness, proportional T1 signal and signal attenuation of the gut wall, as well asthe anterior SUV Max were determined. Next, we used CT, MR, and PET to investigate if animals fed with 5% dextran sulfatesodium(n=14) showed signs of gut inflammation.

RESULTS

Control and Bt-infected animals differed significantly in each diagnostic finding. All diagnostic features were excellent or good withROC-areas of 0.96-0.8 and correlated to each other. We propose contrast-enhanced CT gut wall thickness(sen. 92% and spec. of100%) and MRI gut wall thickness(sen. and spec. of 90%) as key diagnostic findings of gut inflammation in M.sexta. Cryosections ofanimals fed with Bt showed a swollen and fragmented gut wall. Animals fed with DSS showed only significant differences in 3 of 5features suggesting only a moderate gut inflammation. In accordance with this, Bt-fed animals showed a significantly lower survivalcompared to DSS fed animals(p=0.0002). Both groups showed a significantly lower survival(p=0.0001) compared to the controlgroup. Finally, we validated the empirical CT and MRI resolution using gut phantoms and µCT.

CONCLUSION

The M.sexta screening system allows fast screening for new effectors and inhibitors of gut inflammation and could drasticallyreduce vertebrate animal usage in preclinical studies.


The investigation of inhibitors of gut inflammation helps to find new therapies for inflammatory bowel diseases.

ParticipantsAjay Kumar, MD, PhD, Troy, MI (Presenter) Research Grant, Mallinckrodt plcJames G. Granneman, PhD, Detroit , MI (Abstract Co-Author) Nothing to DiscloseOtto Muzik, PhD, Detroit, MI (Abstract Co-Author) Nothing to Disclose

SSK13-05 Irisin Induces White Adipose Tissue Browning in Mice by MR Imaging In Vivo


SSK13-06 Glycosaminoglycan Remodeling of Lumbar Intervertebral Discs in Elite Rowers throughout TheirAnnual Training Cycle



[email protected]

PURPOSE

Recent studies have shown that most adult humans have brown fat cells that could be activated via the adrenergic system. Onceactivated, thermogenesis in these cells could affect the body's energy balance and might be instrumental in weight management.Our objective was to test whether pharmacological stimulation of the adrenergic system using an FDA-approved beta3 agonist(Mirabegron, MRB) is as effective in increasing oxidative metabolism in brown adipose tissue (BAT) as the exposure to mild cold (i.e.non-shivering) temperature.


Six adult lean normal subjects (3F/3M, 24.1 + 4.2 years, BMI = 23.7 + 2.5) underwent 15O-water and 18F-fluorodeoxyglucose(FDG) PET/CT scans either following 1h of cold stress exposure or 3h after MRB intake. Blood flow (ml/100g/min) and glucoseuptake (SUV) were calculated from PET scans at the location of supraclavicular BAT. Changes in whole body daily energyexpenditure (DEE) pre and post cold/MRB was measured using indirect calorimetry. BAT oxygen consumption (MRO2, ml/100g/min)was determined and used to calculate the contribution of cold- or MRB-activated BAT to whole body DEE.

RESULTS

BAT blood flow was found to be significantly higher during cold as compared to MRB intake (16.7 + 7.7 vs. 11.7 + 6.5; p = 0.041),resulting in significantly higher BAT mass during cold (73 + 67g, vs. 53 + 50g, p = 0.048). The ratio between the amount ofpharmacologically activated and cold-activated BAT mass was 0.67 + 0.24. Moreover, MRO2 in BAT was significantly higher duringcold as compared to MRB intake (1.37 + 0.67 vs. 1.0 + 0.49 ml/100g/min, p = 0.044). Overall, the DEE associated with activatedBAT was found to be significantly higher than the DEE linked to MRB activation (7.4 + 5.8 vs. 4.5 + 3.9 kcal/d, p = 0.047).

CONCLUSION

Our findings indicates that activation of BAT using MRB is possible, however to a lesser extent (~2/3) than activations using mildcold exposure. As cold exposure is a more natural way to activate BAT, pharmacological activation of BAT using a beta receptoragonist with possible side effects appears to be a suboptimal method to increase DEE.


The contribution of MRB-activated BAT to whole body energy expenditure is negligible (5 - 15 kcal/d) and as such is unlikely tocontribute to weight loss in subjects that are on a chronic MRB regimen.

ParticipantsYue Chen, BMedSc, Nanjing, China (Presenter) Nothing to DiscloseYufei Zhao, Nanjing, China (Abstract Co-Author) Nothing to DisclosePeng Xingui, Nanjing, China (Abstract Co-Author) Nothing to Disclose


[email protected]

PURPOSE

Our study was to evaluate the browning process of Irisin on white adipose tissue (WAT) using MR imaging in vivo.


After cultured white adipocytes were treated by different concentrations (0, 20 and 40nM, 24 hours), immunohistochemistry andwestern blotting (UCP 1 and DIO 2, the specific protein of brown adipocyte) were used to evaluate the browning of whiteadipocyte. After intraperitoneal injection of Irisin (200ng/d each) and saline (200ul each) into female C57BLKS/J mice (n=7, 10-12w), T1 weighted imaging and chemical shift selective imaging (CSSI) were performed at pre-injection and 14 days post-injectionto measure the volume of WAT and the signal-noise ratio (SNR) of WAT in selective fat imaging of CSSI. Browning of WAT in MRIwere compared to reference standard by histological white adipocyte area in H&E, immunohistochemistry and western blotting.

RESULTS

Primary white adipocytes were successfully cultured and induced to mature. After the intervention of Irisin, the expression levels ofUCP 1 and DIO 2 proteins in white adipocytes increased significantly with the increase of the Irisin concentration. The volume ofsubcutaneous, visceral and total WAT after Irisin intervention by MRI was significantly lower than that of the controls. The SNR ofWAT was lower than that of control, which to indicate the lipid fraction decrease and browning of WAT after Irisin injection(Figure). The area of white adipocytes in Irisin group were significantly lower than that of the controls, and the expression levels ofUCP1 and Dio2 proteins were also significantly increased.

CONCLUSION

Our study was demonstrated that MR imaging could non-invasively assess browning of WAT after Irisin intervention in mice. Irisinnot only reduced the volume of WAT, but also further decreased lipid fraction of WAT.


Irisin can play a potential role in activation of browning of WAT and can be a new therapeutic target in metabolic diseases. MRimaging will play an important monitor role in this process.

SSK13-07 Visceral Fat Browning in a Murine Model Detected by Z-Spectrum Imaging


SSK13-08 Granzyme B PET Imaging to Assess Innate Immune Responses


ParticipantsMiriam Frenken, Dusseldorf, Germany (Presenter) Nothing to DiscloseDaniel B. Abrar, MD, Dusseldorf, Germany (Abstract Co-Author) Nothing to DiscloseLaszlo Kasprowski, Dusseldorf, Germany (Abstract Co-Author) Nothing to DiscloseBernd Bittersohl, MD, Bern, Switzerland (Abstract Co-Author) Nothing to DiscloseGerald Antoch, MD, Dusseldorf, Germany (Abstract Co-Author) Nothing to DiscloseChristoph Schleich, MD, Dusseldorf, Germany (Abstract Co-Author) Nothing to Disclose

PURPOSE

To assess the glycosaminoglycan (GAG) content of lumbar intervertebral discs (IVD) in elite rowers (ER) at different stages of theirannual training cycle and compared to healthy volunteers (HV) using GAG chemical exchange saturation transfer (gagCEST).


205 lumbar IVD of 21 ER (23 ±3 years, 9 female, 11 male) and 25 HV (27 ±2 years, 13 female, 12 male) were prospectivelyexamined with 3T magnetic resonance imaging (MRI). Standard T2 weighted (T2w) sequences were used for morphological gradingaccording to the Pfirrmann classification. GAG content of the nucleus pulposus (NP) and annulus fibrosus was determined withgagCEST in non-degenerated discs according to Pfirrmann. ER were examined during the peak of their competition preparation (T0)and 6 months later during the peak of their post-competition recovery period (T1).

RESULTS

At T0 we found significantly higher gagCEST values in ER compared to HV (NP: 4.26 ±2.37% vs. 3.38 ±1.72%, p<0.05; confidenceinterval (CI) 0.32%/1.44%; AF: 2.75 ±1.7% vs.1.961 ±1.23%, p<0.01; CI 0.4%/1.2%). At T1 gagCEST values decreased andillustrated no significant difference compared to HV (NP: 3.55 ± 2.31%, p = 0.531, CI 0.038%/0.73%; AF: 2.31 ±1.57%, p = 0.073,CI 0.03%/0.74%).

CONCLUSION

Compared to HV lumbar IVD of ER show significantly higher gagCEST values during the peak of their competition preparation andsimilar values during the recovery period, indicating a GAG remodelling effect by training.


Physical exercise (rowing) potentially prevents molecular GAG depletion in lumbar IVD.

ParticipantsAlessandro Scotti, Chicago, IL (Abstract Co-Author) Nothing to DiscloseVictoria Gil, Chicago , IL (Abstract Co-Author) Nothing to DiscloseWeiguo Li, Chicago, IL (Abstract Co-Author) Nothing to DiscloseChong Wee Liew, Chicago, IL (Abstract Co-Author) Nothing to DiscloseKejia Cai, PhD, Chicago, IL (Presenter) Nothing to Disclose

PURPOSE

Conversion of visceral fat into brown fat (browning) is highly beneficial in reducing the risk of metabolic disease, but its study islimited by resistance to conventional browning stimuli and inadequate noninvasive imaging [1,2,3]. Here we report the successfuldetection of white adipose tissue browning in a transgenic mouse model by measurement of depots size and fat-water fraction(FWF) from longitudinal Z-Spectrum MRI.


The transgenic murine model was developed by ablation of the transcriptional regulator TRIP-Br2 (TRIP-Br2 KO mice) [4] andtreated IP with 1mg/Kg of ß3-AR agonist CL316,243 every day for two weeks. Age-matched wild types were treated with saline.Animals underwent MRI at a 9.4T scanner before and 4, 10 and 15 days after treatment start. The size of the perirenal depots wasmeasured on multislice T2-weighted sequences. Z-Spectrum Imaging was performed with a CEST sequence with a single slice FSEreadout. Z-spectral data were fitted to a multi-Lorentzian model including the direct saturation of both water and fat and the FWFwas quantified from the fitted amplitudes in every pixel [3].

RESULTS

ROI analysis showed that the perirenal fat depots decreased in size over time in the KO mice, with volumes shrinking from11.7±1.9mm3 before treatment to 6.9±2.4mm3 after two weeks, compared to the wild types. FWF also was found decreased in thedrug treated mice compared to the control group, with differences between the groups in perirenal fat up to 15% alreadydetectable after 4 days, and increased to 20% at ten days, but decreased at 2 weeks. The changes are consistent with increasedperfusion and reduced lipid content, markers of brown-like cells activation. Also subcutaneous fat showed a sustained decrease inFWF, reaching an average of 25% at the end of the study, but with a higher variability. The different timeline of changes in the fatdepots might indicate a hierarchy to the activation mechanism [5].

CONCLUSION

ZSI has proven to be able to detect browning of white adipose tissue in a murine model chronically treated with adrenergic drug.


Visceral fat is associated with high risk of metabolic disease and is resistant to conventional browning stimuli. Monitoring itsbrowning will be instrumental in combating epidemic metabolic diseases.

SSK13-09 Loss of Glycosaminoglycans of Lumbar Intervertebral Discs in Patients With Ankylosing Spondylitis

Wednesday, Dec. 4 11:50AM - 12:00PM Room: S505AB

ParticipantsKathleen M. Capaccione, MD,PhD, New York, NY (Presenter) Nothing to DiscloseAndrei Molotkov, MD,PhD, New York, NY (Abstract Co-Author) Nothing to DiscloseMikhail Doubrovin, MD, Memphis, TN (Abstract Co-Author) Spouse, Consultant, ATARA Biotherapeutics LtdAkiva Mintz, MD, PhD, Paramus, NJ (Abstract Co-Author) Consultant, Regeneron Pharmaceuticals, Inc

PURPOSE

Granzyme B is a serine protease released by active CD8+ T cells, macrophages and natural killer cells that facilitates granule-mediated apoptosis. Prior studies have demonstrated the utility of granzyme B PET imaging of CD8+ T cells to assess adaptiveimmunity in response to immunotherapy. Our goal is to examine the potential of granzyme B PET imaging as a biomarker of theinnate immune system, which can expand its use for imaging T-cell independent diseases as well as the initial innate immune triggerof an adaptive immune response.


Athymic nude mice were injected in the left shoulder with lipopolysaccharide (LPS) in Matrigel to induce a T-cell independentimmune response. Seventy-two hours later we injected 68Ga-NOTA-GZP as previously reported and performed PET/CT imaging onehour after injection.

RESULTS

PET-CT demonstrated specific binding of the 68Ga-NOTA-GZP at the site of LPS injection within the left shoulder when comparedto control animals injected with PBS. Nonspecific uptake was also seen in the liver and the bladder, suggesting routes ofelimination.

CONCLUSION

Specific 68Ga-NOTA-GZP accumulation at the site of LPS injection in T cell deficient animals supports the use of granzyme B PETimaging for innate immune responses. Future studies will examine the role of granzyme B imaging in specific disease states mediatedby innate immunity.


Granzyme B PET imaging may aide the early diagnosis and evaluation of disease progression of infection and inflammation mediatedby the innate immune system.

ParticipantsDaniel B. Abrar, MD, Dusseldorf, Germany (Presenter) Nothing to DiscloseMiriam Frenken, Dusseldorf, Germany (Abstract Co-Author) Nothing to DiscloseStyliani Tsiami, Herne, Germany (Abstract Co-Author) Nothing to DisclosePhilipp Sewerin, Dusseldorf, Germany (Abstract Co-Author) Nothing to DiscloseLaszlo Kasprowski, Dusseldorf, Germany (Abstract Co-Author) Nothing to DiscloseXenofon Baraliakos, MD, Herne, Germany (Abstract Co-Author) Nothing to DiscloseGerald Antoch, MD, Dusseldorf, Germany (Abstract Co-Author) Nothing to DiscloseChristoph Schleich, MD, Dusseldorf, Germany (Abstract Co-Author) Nothing to Disclose

PURPOSE

To evaluate the glycosaminoglycan (GAG) content of lumbar intervertebral discs (IVD) in patients with ankylosing spondylitis (AS)using GAG chemical exchange saturation transfer (gagCEST).


195 lumbar IVD of 15 patients with AS (mean age 50 ±10 years) and 25 healthy control patients (HC) were prospectively examinedwith 3 T magnetic resonance imaging (MRI). MRI protocol contained morphological T2 weighted (T2w) images to grade IVDaccording to the Pfirrmann classification and biochemical imaging with gagCEST to calculate a region of interest (ROI) of thenucleus pulposus (NP) and annulus fibrosus (AF). Prior to statistical testing of gagCEST effects in patients and HC, IVD wereclassified according to Pfirrmann.

RESULTS

Significantly lower gagCEST values of NP and AF were found in non-degenerative IVD (Pfirrmann 1 and 2) of AS patients comparedto HC (NP: 1.88 % ±1.21% vs. 3.38 % ±1.71%; p<0.01; confidence interval (CI): 0.89%/2.11%. AF: 1.11 % ± 1.07 % vs. 1.96 %±1.23 %; p<0.01; CI 0.39%/1.3%).

CONCLUSION

GagCEST analysis of morphologically non-degenerative IVDs in T2w images showed significantly lower GAG values in patients withAS in the NP and AF compared to HC.


Our results potentially allow for the detection of GAG loss prior to morphological degeneration.


MI211-SD-WEA1

A Multi-Site Phantom Study to Quantify Variation of Hypoxic Fraction Measurement with PET

Station #1

MI223-SD-WEA2

Whole-Body DWI in Lymphoma - First Order Global ADC Histogram Parameters Discriminate

MIS-WEA

Molecular Imaging Wednesday Poster Discussions

Wednesday, Dec. 4 12:15PM - 12:45PM Room: MI Community, Learning Center

MI


ParticipantsGerard N. Bischof, PhD, Cologne, Germany (Moderator) Nothing to Disclose

Sub-Events

ParticipantsIvan Yeung, PHD, Toronto, ON (Presenter) Nothing to DiscloseBrandon Driscoll, MENG, Toronto, ON (Abstract Co-Author) License agreement, Shelley Medical Imaging TechnologiesCarlos Uribe, Vancouver, BC (Abstract Co-Author) Nothing to DiscloseMikalai Budzevich, PHD, Tampa , FL (Abstract Co-Author) Nothing to DiscloseMilan Grkovski, PHD, New York, NY (Abstract Co-Author) Nothing to DiscloseCharles R. Schmidtlein, PhD, New York, NY (Abstract Co-Author) Nothing to DiscloseYoganand Balagurunathan, PhD, Tampa, FL (Abstract Co-Author) Nothing to DiscloseTing-Yim Lee, MSc, PhD, London, ON (Abstract Co-Author) License agreement, General Electric Company; License agreement,Neusoft Digital Medical Systems Co, LtdFiona Li, BS, London, ON (Abstract Co-Author) Nothing to DiscloseSadek A. Nehmeh, PhD, New York, NY (Abstract Co-Author) Nothing to DiscloseSara Zein, New York , NY (Abstract Co-Author) Nothing to DiscloseJohn Sunderland, PhD, Iowa City, IA (Abstract Co-Author) Research Grant, Siemens AG Research Grant, General Electric CompanyDavid A. Jaffray, PhD, Toronto, ON (Abstract Co-Author) Research Grant, Koninklijke Philips Electronics NV Research Grant, ElektaAB Research Grant, Raysearch Laboratories AB Research Grant, IMRIS Inc Research Grant, Varian Medical Systems, Inc ResearchGrant, Modus Medical Devices Inc Royalties, Raysearch Laboratories AB Royalties, Modus Medical Devices Inc Royalties, Elekta ABRoyalties, IMRIS Inc


[email protected]

PURPOSE

'Hypoxic fraction' (HF) calculation in PET hypoxia imaging relies on counting the number of voxels above a predetermined uptakethreshold in the tumor. However, there is no consensus on how to choose the threshold. This work is to test the effect on HFvalues with 2 thresholding methods, namely, a fixed and a statistical threshold.


We ran a study with a 'hypoxia standardization phantom' to quantify the variation of HF measurements over 9 PET-CT and 1 PET-MR scanners at 7 sites in the QIN CT-PET Working Group. The phantom was made of an insert placed in a NEMA IEC PET bodyphantom shell. The insert was constructed with 4 cylindrical columns, aligned with 2 mm solid polycarbonate rods in the cylindricaldirection in predetermined patterns. A 40% uniformly filled pattern is used as 'reference'. As the phantom was filled with 80-100MBq of pure 18F or FDG, the rod patterns would give different averaged activity concentrations in the 3 remaining 'tumor' regionson the PET image simulating tumor uptake in a FMISO or FAZA study. Each participating site did the scan and reconstructionaccording to 2 imaging and 3 reconstruction protocols. The central site performed a preliminary analysis on HF using (i) a statisticalthreshold of mean + 3 s.d. of reference distribution, and (ii) a fixed threshold of 1.2 times the mean of reference distribution.

RESULTS

For a 'typical' clinical imaging and reconstruction protocol, phantom images across the 10 scanners exhibit differences inbackground signal-to-noise ratio (S/N) ranging from 9.2 to 24.3. Among the scanners, variations of HV for the same 'tumors' aregreater for the statistical threshold than for the fixed threshold. HFs range from 20 to 98%, 14 to 90% and 10 to 73% respectivelyover 'tumor' 1, 2 and 3 respectively for the statistical threshold; the corresponding ranges are 66 to 91%, 47 to 90% and 20 to60% for the fixed threshold.

CONCLUSION

The preliminary results show a large range of S/N on images of similar protocols among the scanners. HFs calculated with the fixedthreshold have less variation among these scanners than those of the statistical threshold. Further analysis might lead to a morerobust method for HF calculation.


There is a marked scanner dependent variation in HF measurement with 18F-labelled nitroimidazole-based isotopes; harmonizationof scanners and using a fixed threshold might reduce such variation.

Lymphomatous Nodes from Normal Lymph Nodes

Station #2

MI224-SD-WEA3

Can Whole-Body MRI Help to Improve the Assessment of the Bone Scan 'Flare Effect' in Patients withProstate Bone Metastases?

Station #3

ParticipantsRicardo Donners, MD, Basel, Switzerland (Presenter) Nothing to DiscloseDow-Mu Koh, MD,FRCR, Sutton, United Kingdom (Abstract Co-Author) Nothing to DiscloseRaphael Yiin Shih Zhu, Singapore, Singapore (Abstract Co-Author) Nothing to DiscloseKatja N. De Paepe, MD, Leuven , Belgium (Abstract Co-Author) Nothing to DiscloseSue S. Chua, MBBS, Sutton, United Kingdom (Abstract Co-Author) Nothing to DiscloseIan Chau, Sutton, United Kingdom (Abstract Co-Author) Nothing to DiscloseMatthew Blackledge, PhD, Sutton, United Kingdom (Abstract Co-Author) Nothing to Disclose


[email protected]

PURPOSE

To discriminate lymphomatous from normal lymph nodes using first order general ADC (gADC) histogram parameters derived fromwhole-body DWI (WB-DWI).


WB-DWI of 23 lymphoma patients and 20 healthy individuals, performed on a 1.5T MRI system were reviewed retrospectively. Allmalignant nodal groups of the lymphoma cohort and all nodes visible on b900 images from the neck to groin area of the healthyindividuals were included to generate a total nodal volume (tNV). From the tNV of each patient gADC mean, median, skewness,kurtosis, minimum, maximum, interquartile range (IQR), standard deviation (SD), 10th and 90th centile were derived. gADCparameters were compared between lymphomatous and normal nodes using t-tests, a p-value < 0.05 was deemed significant. Thediscriminatory ability of each significant parameter was assessed by ROC curve analyses.

RESULTS

Mean, median, 10th and 90th centiles gADC values were significantly lower in lymphomatous than in normal lymph nodes (each p <0.001). tDV, gADC skewness and kurtosis were significantly higher in lymphomatous nodes (each p < 0.05). The SD, min and maxgADC showed no significant difference (each p > 0.128). The order of maximum diagnostic accuracy of gADC parameters asindicated by the AUC from highest to lowest was: 10th centile, mean, median, 90th centile, skewness, kurtosis and IQR. A 10thcentile gADC threshold of 0.68 x 10-³ mm²/s identified lymphomatous nodes with 91% sensitivity and 95% specificity.

CONCLUSION

gADC histogram parameters derived from WB-DWI allow discrimination between lymphomatous and normal lymph nodes.


WB-DWI can distinguish lymphomatous from normal lymph nodes.

ParticipantsFilippo Pesapane, MD, Milan, Italy (Presenter) Nothing to DiscloseDow-Mu Koh, MD,FRCR, Sutton, United Kingdom (Abstract Co-Author) Nothing to DiscloseGiorgio Maria Agazzi, Brescia, Italy (Abstract Co-Author) Nothing to DiscloseDiletta Bianchini, London, United Kingdom (Abstract Co-Author) Nothing to DisclosePasquale Rescigno, London, United Kingdom (Abstract Co-Author) Nothing to DiscloseNina Tunariu, MD, Sutton, United Kingdom (Abstract Co-Author) Nothing to Disclose


[email protected]

PURPOSE

The assessment of treatment response of prostate bone metastases using bone scintigraphy is confounded by the 'flare effect',which can be misinterpreted as disease progression. We aim to evaluate the response categorization by whole body MRI (WB-MRI)in patients with suspected 'flare effect' on bone scintigraphy at 12 weeks after therapy.


Ten patients (mean age at baseline evaluation: 73.5+/-10) with metastatic prostate cancer demonstrating at least two news bonelesions at bone scintigraphy at 8 to 12 weeks after initiating treatment compared with baseline imaging; who also had WB-MRIincluding DWI at baseline and at 8 to 12 weeks after therapy were identified by search of electronic health record. The WB-MRIimages were reviewed by an expert radiologist with > 10 year experience and response categorized according to MET-RADS-Pcriteria (score 1-5; 1 = definite response, 5 = definite progression). The bone scintigraphy were evaluated using the ProstateCancer Working Group criteria that require a subsequent confirmatory bone scintigraphy performed at 6-12 weeks. The soft tissuedisease was evaluated using RECIST 1.1.

RESULTS

Disease sites in the 10 patients were bone only (n=6), bone and soft tissue (nodal n=3 and liver n=1). At follow-up, 3 patients hadprogressive disease by RECIST 1.1, treatment was stopped and no confirmatory bone scintigraphy was performed. In the 7 patientswith subsequent confirmatory bone scintigraphy (week 24 of therapy), the outcome based on PCWG criteria was: A) FLARE (n=2)B) Progression (n=3) and C) Non evaluable due to malignant superscan (n=2). The corresponding 8-12 week WBMRI evaluation was:A) Response (n =1 of 2) and Discordant response (n=1 of 2) ; B) Progression (n=3 of 3) and C) Progression (n=1 of2) and Response(n=1 of 2).

CONCLUSION

WB-MRI at 8-12 weeks of therapy can help to better categorize responders and non-responders earlier in patients with prostatebone metastases differentiating the flare effect from disease progression on bone scintigraphy, as well as identifying discordantresponse between disease sites.


The use of WB-MRI can help to overcome the diagnostic pitfall of the 'flare response' on bone scintigraphy when patients withprostate bone metastases undergo treatment.


MI212-SD-WEB1

The Slow Component Apparent Diffusion Coefficient (ADC) is Replaced by Washout of the DynamicContrast Enhancement (DCE) Study for Prostate Cancer

Station #1

MI225-SD-WEB2

18F-FMISO PET May Be Applicable in The Evaluation of Colorectal Cancer Liver Metastasis

Station #2

MIS-WEB

Molecular Imaging Wednesday Poster Discussions

Wednesday, Dec. 4 12:45PM - 1:15PM Room: MI Community, Learning Center

MI


ParticipantsGerard N. Bischof, PhD, Cologne, Germany (Moderator) Nothing to Disclose

Sub-Events

ParticipantsAkio Ogura, PhD, Maebashi, Japan (Abstract Co-Author) Nothing to DiscloseFumie Maeda, Kyoto, Japan (Presenter) Nothing to DiscloseSeiji Yahata, Tokyo, Japan (Abstract Co-Author) Nothing to DiscloseNorio Hayashi, PhD, Maebashi, Japan (Abstract Co-Author) Nothing to DiscloseFumiya Tsunoda, Ashikaga , Japan (Abstract Co-Author) Nothing to DiscloseDaisuke Koyama, Nagano, Japan (Abstract Co-Author) Nothing to DiscloseKenichiro Yamamura, Takatsuki, Japan (Abstract Co-Author) Nothing to DiscloseShunichi Motegi, Gunma, Japan (Abstract Co-Author) Nothing to Disclose

PURPOSE

A purpose of this study is to obtain relations of the slow component ADC and the wash out index of dynamic contrast enhancedimaging of prostate cancer.


Diffusion-weighted and dyanmic contrast enhanced image were obtained from 39 patients with prostate cancer from 4 differentinstitutions. The fast component ADC was calculated at b-values from 0 and 1000 s/mm2. and the slow component ADC wascaluculated at b-values from 1000 and 2000 s/mm2. Regions of interest were set to the tumor legion and the contralateral normallesionn, and slow component ADC index and wash-out index were calculated. The correlations between the wash-in and wash-outrates for dyanamic contrast enhanced imaging, and the fast and sloe ADCs for DWI were compared.

RESULTS

The coefficient of correlation of wash-out index and slow component ADC was 0.73, and the fast component ADC was 0.35.

CONCLUSION

A high correlation was shown between slow component ADC and the wash-out index. It has been already reported that there is ahigh correlation between IVIM and the fast component ADC. Therfore, the IVIM index and the slow component ADC by multi-b-values DWI can be substituted by the indices for dynamic contrast enhanced imaging. However, the choice for the b-values isimportant and optimal b-values should be chosen for an effective numerical value, in terms of diagnosis and shortening imagingtime.


This research indicates that patients can obtain equvalent diagnosis results without the contrast media on the examination of theprostate. This is extremely usuful in safety and the costs of the patients.

ParticipantsHuijie Jiang, PhD, MS, Harbin, China (Presenter) Nothing to Disclose


[email protected]

PURPOSE

Positron emission tomography (PET) imaging is a non-invasive functional imaging method used to reflect tumor spatial information,and to provide biological characteristics of tumor progression. The aim of this study was to focus on the application of 18F-fluoromisonidazole(FMISO) PET quantitative parameter of maximum standardized uptake value (SUVmax) ratio to detect the livermetastatic potential of human colorectal cancer in mice.


Wound healing assays were performed to examine the ability of cell migration in vitro. 18F-FMISO uptake in CRC cell lines wasmeasured by cellular uptake assay. 18F-FMISO-based micro-positron emission tomography imaging of colorectal liver metastasis and

MI226-SD-WEB3

Knowing the Unknown-Utility of FDG PET CT in Evaluation of Pyrexia of Unknown Origin-PUO

Station #3

tumor-bearing mice was performed and quantified by tumor-to-liver SUVmax ratio. The correlation between the 18F-FMISO SUVmaxratio, liver metastases number, hypoxia-induced HIF-1a and serum starvation-induced GLUT-1 was evaluated using Pearsoncorrelation analysis.

RESULTS

Compared with HT29 and HCT116, LoVo-CLM mice had significantly higher liver metastases ratio and shorter median survival time.LoVo cells exhibited stronger migration capacity and higher radiotracer uptake compared with HT29 and HCT116 in in vitro.Moreover, 18F-FMISO SUVmax ratio was significantly higher in both LoVo-CLM model and LoVo-bearing tumor model compared tomodels established using HT29 and HCT116. In addition, a linear regression analysis revealed a significant correlation between 18F-FMISO SUVmax ratio of CLM-mice and number of liver metastases larger than 0.5cm, as well as between 18F-FMISO SUVmax ratioand HIF-1a or GLUT-1 expression in tumor-bearing tissues.

CONCLUSION

18F-FMISO parameter of SUVmax ratio may provide useful tumor biological information in mice with CRC liver metastasis, thusallowing for better prediction of CRC liver metastasis and yielding useful radioactive markers for predicting liver metastasis potentialin CRC.


Better prediction of CRC liver metastasis and yielding useful radioactive markers for predicting liver metastasis potential in CRC.

ParticipantsNikita K. Jain, MBBS,MD, Bangalore, India (Presenter) Nothing to DiscloseShivakumar Swamy Shivalingappa, DMRD,MBBS, Bangalore, India (Abstract Co-Author) Nothing to DiscloseIndiresh N. Desai, MBBS, DMRD, Bangalore, India (Abstract Co-Author) Nothing to DiscloseKumar Kallur, MBBS, MD, Bangalore , India (Abstract Co-Author) Nothing to DiscloseMahesh Ashok Kumar, MD,MBBS, Bangalore, India (Abstract Co-Author) Nothing to DiscloseAvinash R. Kesari, Bangalore , India (Abstract Co-Author) Nothing to DiscloseSudhakar Sampangi, DMRD, Bangalore, India (Abstract Co-Author) Nothing to DiscloseYashaswini K. Kumaraswamy, Bangalore , India (Abstract Co-Author) Nothing to DisclosePrashanth G.R, Bangalore, India (Abstract Co-Author) Nothing to DiscloseRajkumar K, Bangalore , India (Abstract Co-Author) Nothing to Disclose


[email protected]

PURPOSE

This study aims to study the utility/ diagnostic performance of FDG PET CT in patients with PUO.


Retrospective review of PET CT scans of 74 patients with PUO (mean age- 24 to 60) from jan 2017 to jan 2019 was performed .FDG PET CT was performed in these cases after inconclusive conventional imaging. FDG PET-CT was performed after injecting theFDG contrast and scan done after 60 minutes. FDG uptake was evaluated based on SUV max. Final diagnosis was based onLaboratory tests ,biopsy and imaging follow-up.

RESULTS

Out of 74 cases, FDG showed positive findings in 61 cases (82.4%). The FDG PET CT findings in positive cases were - 23 infection,15 malignancy, 15 noninfectious inflammatory diseases and 8 other non specific findings. PET CT scan was done on an average atday 10(+/-5 days).Most commonly seen infection was tuberculosis in 70% of cases. Most commonly seen malignancy waslymphoma in 12 out of 15 cases (80%). Other malignancies identified included hematologic malignancies and multiple myeloma.Amongst the non infective inflammatory conditions like sarcoidosis, Castleman s disease and other granulomatous diseases wereseen. Other non specific findings on PET CT included colitis, thyroiditis, vasculitis etc. Results Table: True Positive in 52 /74 cases.False Positive lesions in 9/74, due to reactive nodes confirmed with subsequent CT. True Negative lesions in 9/74, clinically self-limiting conditions with full spontaneous recovery. Such spontaneous recovery took 14 days on average (+/- 18 days) after hospitaladmission. False Negative lesions in 4/74. The sensitivity of PET CT was 92%, PPV was 85%.

CONCLUSION

Thus 18F-FDG PET-CT could help in identifying the cause in 85% of cases. A negative PET-CT with no spontaneous recovery stillrequires further investigations in order to exclude various causes such as non FDG avid small gastrointestinal/renal/pancreaticmalignancies.


FDG PET CT is one of the most valuable imaging tool in finding the unknown in PUO.


SSM16-01 Prospective Evaluation of the First Integrated PET/Dual-Energy CT System in Patients with LungCancer

Wednesday, Dec. 4 3:00PM - 3:10PM Room: S505AB

SSM16

Molecular Imaging (Oncology)


MI OI



ParticipantsPedram Heidari, MD, Charlestown, MA (Moderator) Nothing to DiscloseBenjamin Larimer, PhD, Charlestown, MA (Moderator) Co-founder, Cytosite Biopharma Inc; Consultant, Cytosite Biopharma Inc;Stockholder, Cytosite Biopharma Inc

Sub-Events

AwardsTrainee Research Prize - Resident

ParticipantsSimon S. Martin, MD, Charleston, SC (Presenter) Institutional Research support, Siemens AGMarly van Assen, MSc, Charleston, SC (Abstract Co-Author) Nothing to DisclosePhilip Burchett, MSc, Charleston, SC (Abstract Co-Author) Nothing to DiscloseJames G. Ravenel, MD, Charleston, SC (Abstract Co-Author) Consultant, ImBio, LLCLeonie Gordon, MBChB, Charleston, SC (Abstract Co-Author) Nothing to DiscloseCarlo N. De Cecco, MD, Atlanta , GA (Abstract Co-Author) Research Grant, Siemens AGAkos Varga-Szemes, MD, PhD, Charleston, SC (Abstract Co-Author) Research Grant and Travel Support, Siemens AG ResearchConsultant, Elucid BioimagingThomas J. Vogl, MD, PhD, Frankfurt , Germany (Abstract Co-Author) Nothing to DiscloseU. Joseph Schoepf, MD, Charleston, SC (Abstract Co-Author) Research Grant, Astellas Group; Research Grant, Bayer AG; ResearchGrant, Bracco Group; Research Grant, Siemens AG; Research Grant, Heartflow, Inc; Research support, Bayer AG; Consultant, ElucidBioImaging Inc; Research Grant, Guerbet SA; Consultant, HeartFlow, Inc; Consultant, Bayer AG; Consultant, Siemens AG; ; ;


[email protected]

PURPOSE

The aim of this study was to prospectively evaluate the first integrated positron emission tomography (PET)/ dual-energy computedtomography (DECT) system in patients with small-cell lung cancer (SCLC) or non-small-cell lung cancer (NSCLC).


In this single-center HIPAA compliant prospective trial, we included 25 patients (age range, 41-84 years; median age, 62 years)with NSCLC (n=21) or SCLC (n=4) who were referred for a PET/CT study between May 2017 and June 2018. All patients receivedcontrast-enhanced imaging on a clinical PET/DECT system 70 min after the administration of 5MBq/kg of 18F-fluorodeoxyglucose(18F-FDG). Data analysis included PET-based standard uptake values (SUVmax) and DECT-based iodine densities of tumor massesand lymph nodes. Results between the different parameters were compared using Pearson correlation analysis and receiveroperating characteristics (ROC) analysis.

RESULTS

SUVmax and iodine density parameters were measured in 33 malignant lung masses (15.0 and 2.3 mg/mL, respectively) and 56enlarged mediastinal or hilar lymph nodes (8.4 and 2.2 mg/mL, respectively). A moderate correlation was found for SUVmax andiodine density values in tumor masses (r=0.53). SUVmax and iodine density values of lymph node metastases showed a weakcorrelation (r=0.36). Additionally, iodine quantification analysis provided no added value for the differentiation of malignant frombenign lymph nodes with an area under the curve (AUC) of 0.52 using PET-based SUVmax analysis as the reference standard.

CONCLUSION

The integration of PET/DECT information in lung cancer staging can provide additional insights in the assessment of primary lungcancer and on the correlation between tumor vascularization and metabolic activity, offering an alternative for tumorcharacterization improvements. However, the weak correlation between SUVmax and iodine density in malignant lymph nodessuggest that iodine density alone has a limited value for lymph node characterization.


This is the first clinical study on an integrated PET/DECT which provides additional insights in the assessment of lung cancer,offering an alternative for tumor characterization improvements.

SSM16-02 Deep Learning for Prostate Cancer Lymph Node Staging: Balance and Location Matter


SSM16-03 18F-FMISO PET May Be Applicable in The Evaluation of Colorectal Cancer Liver Metastasis


ParticipantsAlexander Hartenstein, Berlin, Germany (Abstract Co-Author) Nothing to DiscloseFalk Lubbe, Berlin, Germany (Abstract Co-Author) Nothing to DiscloseBernd K. Hamm III, MD, Berlin, Germany (Abstract Co-Author) Research Consultant, Canon Medical Systems Corporation;Stockholder, Siemens AG; Stockholder, General Electric Company; Research Grant, Canon Medical Systems Corporation; ResearchGrant, Koninklijke Philips NV; Research Grant, Siemens AG; Research Grant, General Electric Company; Research Grant, Elbit ImagingLtd; Research Grant, Bayer AG; Research Grant, Guerbet SA; Research Grant, Bracco Group; Research Grant, B. Braun MelsungenAG; Research Grant, KRAUTH Medical KG; Research Grant, Boston Scientific Corporation; Equipment support, Elbit Imaging Ltd;Investigator, CMC Contrast ABMarcus R. Makowski, Berlin, Germany (Abstract Co-Author) Nothing to DiscloseTobias Penzkofer, MD, Berlin, Germany (Presenter) Researcher, AGO; Researcher, Aprea AB; Researcher, Astellas Group;Researcher, AstraZeneca PLC; Researcher, Celgene Corporation ; Researcher, Genmab A/S; Researcher, Incyte Coporation;Researcher, Lion Biotechnologies, Inc; Researcher, Takeda Pharmaceutical Company Limited; Researcher, Morphotec Inc;Researcher, Merck & Co, Inc; Researcher, Tesaro Inc; Researcher, F. Hoffmann-La Roche Ltd;


[email protected]

PURPOSE

To evaluate if PSMA-PET lymph node status can be predicted using deep convolutional networks (CNN) from CT imaging alone andassess the influence of class balancing and anatomical context on classification results compared to radiologists' performance.


549 patients, who had received 68Ga-PSMA PET/CT examination, were included. 2616 lymph nodes (LN) were segmented on CT,the corresponding status was determined from PSMA-PET/CT. Two training datasets were used: The first set ('naively balanced',NB) was created by balancing the infiltration status alone. The second set ('location balanced', LB), was created by additionallybalancing within each anatomical region. 130 nodes were set aside for independent testing, leaving 732 (NB) and 548 nodes (LB)after balancing. Three CNNs were created, the first two trained with contrast-enhanced CT images and segmentations of either NBor LB test sets respectively, while the third received masked CT images of the NB set (xMask). All networks were analysed for theirtest set performance (vs. two radiologists) and heatmap patterns.

RESULTS

The NB trained CNN performed best, with an AUC of 0.955 (95% CI 0.923-0.987). The LB and xMask trained CNN performedcomparably well, with AUCs of 0.858 (LB, 95% CI 0.793-0.922) and 0.863 (xMask, 95% CI 0.804 - 0.923). The radiologists achievedan average AUC, sensitivity, specificity and accuracy of 0.81, 65%, 96% and 81% respectively. Analyzing the heatmaps, activationpatterns suggest, that CNNs learn features within the lymph nodes but also, and more troublingly, outside of the lymph nodes,which correlate to the infiltration status. It is critical to note that our best performing model appears to rely on features outside ofthe lymph node in question, such as the skin/air border often found in the inguinal region, which are rarely infiltrated.

CONCLUSION

Deep Learning systems are prone to learning unknown bias present in data, and efforts should be made to prove that classificationsystems perform as intended. Nevertheless, our results show that CNNs are capable of determining the 68Ga-PSMA PET/CTinfiltration status from PCa on contrast-enhanced CT scans alone.


Careful training of CNNs to predict the PSMA/PET lymph node status from CT alone could add value to non-PET stagingexaminations.

ParticipantsHuijie Jiang, PhD, MS, Harbin, China (Abstract Co-Author) Nothing to DiscloseMingyu Zhang, PhD, harbin, China (Presenter) Nothing to Disclose


[email protected]

PURPOSE

Positron emission tomography (PET) imaging is a non-invasive functional imaging method used to reflect tumor spatial information,and to provide biological characteristics of tumor progression. The aim of this study was to focus on the application of 18F-fluoromisonidazole(FMISO) PET quantitative parameter of maximum standardized uptake value (SUVmax) ratio to detect the livermetastatic potential of human colorectal cancer in mice.


Wound healing assays were performed to examine the ability of cell migration in vitro. 18F-FMISO uptake in CRC cell lines wasmeasured by cellular uptake assay. 18F-FMISO-based micro-positron emission tomography imaging of colorectal liver metastasis andtumor-bearing mice was performed and quantified by tumor-to-liver SUVmax ratio. The correlation between the 18F-FMISO SUVmaxratio, liver metastases number, hypoxia-induced HIF-1a and serum starvation-induced GLUT-1 was evaluated using Pearsoncorrelation analysis.

RESULTS

SSM16-04 Comparison of 18F-DCFPyL-PSMA PET/CT and PET/MR for Detection of Prostate Cancer BiochemicalRecurrence: Additive Value of PyL PET with Pelvic MRI for Salvage Radiation Therapy Planning


SSM16-05 Real-Time 3D Thermography in a Liver Tumor Ablation Model Using Magnetic Particle Imaging


Compared with HT29 and HCT116, LoVo-CLM mice had significantly higher liver metastases ratio and shorter median survival time.LoVo cells exhibited stronger migration capacity and higher radiotracer uptake compared with HT29 and HCT116 in in vitro.Moreover, 18F-FMISO SUVmax ratio was significantly higher in both LoVo-CLM model and LoVo-bearing tumor model compared tomodels established using HT29 and HCT116. In addition, a linear regression analysis revealed a significant correlation between 18F-FMISO SUVmax ratio of CLM-mice and number of liver metastases larger than 0.5cm, as well as between 18F-FMISO SUVmax ratioand HIF-1a or GLUT-1 expression in tumor-bearing tissues.

CONCLUSION

18F-FMISO parameter of SUVmax ratio may provide useful tumor biological information in mice with CRC liver metastasis, thusallowing for better prediction of CRC liver metastasis and yielding useful radioactive markers for predicting liver metastasis potentialin CRC.


Better prediction of CRC liver metastasis and yielding useful radioactive markers for predicting liver metastasis potential in CRC.

ParticipantsEdward M. Lawrence, MD, PhD, Madison, WI (Presenter) Nothing to DiscloseMinnie Kieler, Madison, WI (Abstract Co-Author) Nothing to DiscloseShane A. Wells, MD, Madison, WI (Abstract Co-Author) Consultant, Johnson & JohnsonGreg Cooley, Madison, WI (Abstract Co-Author) Nothing to DiscloseSteve Cho, MD, Madison, WI (Abstract Co-Author) Research Grant, General Electric Company; Consultant, Advanced AcceleratorApplications SA;


[email protected]

PURPOSE

To evaluate prostate specific membrane antigen (PSMA)-based 18F-DCFPyL(PyL) PET in prostate cancer (PC) biochemicalrecurrence (BCR) and benefit for salvage radiation therapy (RT) planning.


Patients with PC history, prior prostatectomy, and planned RT for BCR were prospectively recruited. Three PyL PET studies weredone - whole body PET/CT (wbPET/CT) on a Discovery 710, [pelvic PET/MR (pPET/MR) with multiparameteric pelvic MR (mpMRI),and whole body PET/MR (wbPET/MR) on a Discovery 710 and Signa scanner [GE, Waukesha, WI] respectively. Patients thenunderwent salvage RT. Two readers independently used two proposed PSMA PET evaluation methods (PSMA-RADS v1, PROMISE)for PET evaluation followed by third reader adjudication. Separately, the mpMRI was evaluated for local or pelvic lymph node (LN)recurrence and proposed post-PET treatment was compared to a standard plan using clinical risk and mpMRI. PET positive siteswere evaluated in relation to the actual radiation field.

RESULTS

12 patients (mean age, 61.8 yrs; median pre-RT PSA, 0.92 ng/mL) had 29 PET sites of suspected recurrence. Eight of 12 patients(66%) had a positive PyL PET with suspected disease confined to the pelvis (n=5) or with distant disease (n=3). Positive sites hadconsensus PSMA-RADS scores of 5 (n=15), 4 (n=1), and 3 (n=12) as well as PROMISE miPSMA expression scores of 3 (n=5), 2(n=12), and 1 (n=10). Median maximum standardized uptake value (SUVmax) was 9.5, 6.3, and 5.4 for reader 1 and 9.5, 5.9, and6.1 for reader 2 on pPET/MR, wbPET/MR, and wbPET/CT respectively. pPET/MR detected all PET positive sites within the pelvis.Compared to PyL PET, mpMRI detected 2/4 sites of suspected local recurrences and 1/16 PET positive LNs. Five of 12 patientswould have had a proposed treatment plan change based on PyL PET. One RADS-5 LN and 5 equivocal targets (LN, n=2; rib lesion,n=3) were outside the actual radiation field. Additionally, two RADS-5 LNs were at the edge of the field and would have resulted inextended coverage.

CONCLUSION

PSMA-based PyL PET detected suspicious sites in 66% of BCR patients with highest median SUVmax on pPET/MR. PyL PET resultswould have theoretically changed management in 42% (n=5) patients.


PyL PET was positive in two-thirds of BCR after prostatectomy. PyL PET improves detection of suspected sites of PC recurrenceand could impact patient management and RT treatment field planning.

ParticipantsJohannes M. Salamon, MD, Hamburg, Germany (Presenter) Nothing to DiscloseCaroline Jung, Hamburg, Germany (Abstract Co-Author) Nothing to DiscloseMichael G. Kaul, Hamburg, Germany (Abstract Co-Author) Nothing to DiscloseGerhard B. Adam, MD, Hamburg, Germany (Abstract Co-Author) Nothing to DiscloseTobias Knopp, DIPLENG, Hamburg, Germany (Abstract Co-Author) Nothing to DiscloseHarald Ittrich, MD, Hamburg, Germany (Abstract Co-Author) Nothing to Disclose


[email protected]

SSM16-06 Study of Hypoxia in Pancreatic Cancer Patients Using Dynamic [18F]-FAZA PET


PURPOSE

Evaluation of the feasibility of visualizing the temperature course during a thermal ablation in an in vitro liver tumor phantom usingMPI and different iron oxide tracers.


In vitro liver tissue phantoms with different iron oxide tracers (L93, Bayer-Schering; LS008, Load Spin Labs; MM4, TOPASS GmbH,concentrations of 0.1-0.5 mg/ml) were generated in Eppendorf-Tubes using a 1:1 volume mixture of protein and water (ChickenWhite Protein, Sigma Aldrich). The phantoms were heated by means of an inserted copper wire (1 mm diameter) and MPI-inducededdy currents. The resulting signal changes of the phantom were simultaneously imaged by MPI. As an in vitro liver tumor ablationmodel, tracer-free protein (pseudotumor) was embedded in protein (pseudo-liver tissue) mixed with L93 (CFe = 0.356 mg/ml). Thepseudotumors were heated by means of an inserted copper wire with simultaneous detection of the MPI signal of the surroundingpseudo-liver tissue. All experiments were carried out on a commercial MPI system (Philips/Bruker) using a FoV of 37.3 x 37.3 x 18.6mm3 and a frame rate of 46 frames/s.

RESULTS

Corresponding to the heating, MPI signal increase could be detected in all tracers. L93 showed the highest temperaturechanges/sensitivity. In the liver tumor ablation model, the ablation of the pseudo-liver tissue was visualized in 3D in real time byMPI signal changes.

CONCLUSION

MPI is suitable for visualizing temperature distribution and changes in a liver tumor ablation model. The sensitivity dependsdecisively on the used tracer. A temperature monitoring of healthy tissue for optimized MPI-guided tumor ablation in real time and3D is feasible.


Real time temperature measurement using MPI in the course of an ablation procedure might emerge as a powerful tool for exactmonitoring of ablation success.

ParticipantsFiona Li, BS, London, ON (Abstract Co-Author) Nothing to DiscloseEdward Taylor, Toronto, ON (Abstract Co-Author) Nothing to DiscloseIvan Yeung, PHD, Toronto, ON (Abstract Co-Author) Nothing to DiscloseDavid A. Jaffray, PhD, Toronto, ON (Abstract Co-Author) Research Grant, Koninklijke Philips Electronics NV Research Grant, ElektaAB Research Grant, Raysearch Laboratories AB Research Grant, IMRIS Inc Research Grant, Varian Medical Systems, Inc ResearchGrant, Modus Medical Devices Inc Royalties, Raysearch Laboratories AB Royalties, Modus Medical Devices Inc Royalties, Elekta ABRoyalties, IMRIS IncDavid W. Hedley, MD, Toronto, ON (Abstract Co-Author) Nothing to DiscloseTing-Yim Lee, MSc, PhD, London, ON (Presenter) License agreement, General Electric Company; License agreement, Neusoft DigitalMedical Systems Co, Ltd


[email protected]

PURPOSE

To estimate kinetic parameters of [18F]-FAZA in highly hypoxic pancreatic cancer and determine the sensitivity of theseparameters in distinguishing normal tissue from hypoxic cancer.


Twenty patients with pancreatic ductal adenocarcinoma underwent 55 min of dynamic [18F]-FAZA scan. The tissue time activitycurve (TAC) was analysed using graphical methods - Patlak and Logan plot to determine the reversibility of binding and usingstandard two tissue compartment model (S2TCM) as well as our bespoke kinetic model, the flow modified two tissue compartmentmodel (F2TCM) to estimate the kinetic parameters. F2TCM models mean transit time through blood vessels, which couldsignificantly affect parameter estimations. Multivariate logistic regression was used to find the optimal parameter set fordistinguishing normal tissue from hypoxia tumor.

RESULTS

Graphical analysis showed that the tracer was reversibly bound and distribution volume (DV) determined by S2TCM and F2TCM wascorrelated to that of Logan plot. F2TCM fitted TACs better than S2TCM according to the Akaike Information Criteria. Logisticregression determined that DV and dissociation rate constant (k4) classified normal tissue from hypoxic tumor with sensitivity,specificity and negative predictive value (NPV) of 57%, 95% and 92% respectively while it is lower - 43%, 79 % and 67% forLogan's DV.

CONCLUSION

Contrary to the accepted notion that [18F]-FAZA is irreversibly bound, both graphical and kinetic analysis showed that the bindingis reversible. The proposed mechanism for the reversibility is that the reduced metabolite, amino-FAZA, is conjugated to glutathione(amino-FAZA-GS) which is usually trapped in cells due to its hydrophilicity, however, in the presence of elevated multidrugresistance protein (MRP-1) in pancreatic tumor, amino-FAZA-GS can be 'pumped' out of the cells leading to radioactivity washoutor reversible binding. Besides distinguishing normal pancreatic tissue from hypoxic tumor, kinetic modeling allows evaluation of k4which can be associated with MRP-1 activity, while the binding rate constant (k3) can be associated with nitroreductase andglutathione activity.


Non-invasive monitoring of MRP-1 activity and hence drug resistance for hypoxic tumor with [18F]-FAZA could lead to

Non-invasive monitoring of MRP-1 activity and hence drug resistance for hypoxic tumor with [18F]-FAZA could lead topersonalization of cancer treatment.


ED015-TH

Molecular Imaging Thursday Case of the Day

Thursday, Dec. 5 7:00AM - 11:59PM Room: Case of Day, Learning Center



TEACHING POINTS



SPDL50

Keeping Radiology Weird: Spot Diagnoses from the Pacific Northwest (Case-based Competition)

Thursday, Dec. 5 7:15AM - 8:15AM Room: E451B

GI MI MK NM

AMA PRA Category 1 Credit ™: 1.00ARRT Category A+ Credit: 0

ParticipantsBarry G. Hansford, MD, Chicago, IL (Presenter) Nothing to DiscloseElena K. Korngold, MD, Portland, OR (Presenter) Nothing to DiscloseNadine Mallak, MD, Portland, OR (Presenter) Nothing to Disclose


[email protected]

[email protected]

[email protected]

Special Information

This interactive session will use RSNA Diagnosis Live™. Please bring your charged mobile wireless device (phone, tablet or laptop)to participate.

LEARNING OBJECTIVES

1) Be introduced to a series of musculoskeletal, abdominal radiology and nuclear medicine case studies via an interactive gameapproach designed to encourage "active" consumption of education material. 2) Be able to use their mobile wireless device (tablet,phone, laptop) to electronically respond to various imaging case challenges; participants will be able to monitor their individual andteam performance in real time. 3) Receive a personalized self-assessment report via email that will review the case materialpresented during the session, along with individual and team performance.


SSQ12-01 Molecular Imaging Keynote Speaker: Recent Efforts for the Use of Machine Learning for PET/MRI

Thursday, Dec. 5 10:30AM - 10:50AM Room: S501ABC

SSQ12-03 Addressing Long-Term Fate of Iron Oxide Nanoparticles(ION) and Specific MRI Cell Tracking byCombining MRI and Mass Spectrometry with 57Fe-ION


SSQ12-04 Evaluation of Low Dose PET Simulation Using Time-, Space-, and Order-Based Approaches on a SiPMDigital Photon Counting Time-of-Flight PET/CT

SSQ12

Science Session with Keynote: Molecular Imaging (Image Analysis and Quantification)

Thursday, Dec. 5 10:30AM - 12:00PM Room: S501ABC

BQ MI



ParticipantsCiprian Catana, MD, PhD, Charlestown, MA (Moderator) Nothing to DiscloseDima A. Hammoud, MD, Bethesda, MD (Moderator) Nothing to Disclose

Sub-Events

ParticipantsCiprian Catana, MD, PhD, Charlestown, MA (Presenter) Nothing to Disclose

ParticipantsMax Masthoff, MD, Muenster, Germany (Presenter) Nothing to DiscloseAndre Beuker, Muenster, Germany (Abstract Co-Author) Nothing to DiscloseRebecca Buchholz, Muenster, Germany (Abstract Co-Author) Nothing to DiscloseUwe Karst, PhD, Muenster, Germany (Abstract Co-Author) Nothing to DiscloseWalter L. Heindel, MD, Muenster, Germany (Abstract Co-Author) Nothing to DiscloseCornelius Faber, Muenster, Germany (Abstract Co-Author) Nothing to DiscloseMoritz Wildgruber, MD, PhD, Iffeldorf, Germany (Abstract Co-Author) Nothing to Disclose

PURPOSE

Iron oxide nanoparticles (ION) are common contrast agents for (pre-)clinical MRI, but signal is always influenced by endogenousiron hampering quantification of administered ION. We combine non-radioactive 57Fe-ION MRI with laser-ablation-mass-spectrometry (LA-ICP-MS) for differentiation between endogenous iron (56Fe) and applied ION. We aim to assess distribution andlong-term fate of ION, to correlate ION concentration to T2-relaxivity and to apply 57Fe-ION for cell tracking.


Healthy C57BL/6 mice were injected with custom engineered 57Fe-ION (NanoPET, Berlin). For ION distribution T2-mapping of liver,spleen, kidney and brain was performed on a 9.4T small-animal MRI after 2h, 1d, 3d, 7d, 30d and 90d (n=5 each). For ironamount/T2 correlation mice were injected with increasing ION dosage. Mice were sacrificed and organs extracted for LA-ICP-MS toquantify 57Fe and the 56Fe/57Fe isotope ratio. To evaluate 57Fe-ION for cell tracking mice were injected s.c. with apolyacrylamide-gel (pellet) to induce local inflammation. After 24h first baseline MRI with T2-mapping of the pellet was performed,followed by i.v. injection of either 57Fe-ION or PBS as control (n=3 each). 24h later MRI was repeated followed by histology andLA-ICP-MS.

RESULTS

57Fe-ION MRI with LA-ICP-MS enabled to specifically assess and resolve local distribution and long-term fate of ION. 57Fe of IONwas first found in cells of the reticulo-endothelial-system (RES), but relocated to endogenous iron stores especially in spleen, bloodand brain parenchyma after 90d. A non-linear dependence of T2-relaxivity on increasing ION dosage was observed in the liver, likelyresulting from ION packing and state during metabolic processing. T2-relaxivity in the cell tracking model was mainly influenced byapplied 57Fe-ION, which were located in adjacent inflammatory tissue representing invaded labelled cells, and not by endogenousiron sources.

CONCLUSION

Combining 57Fe-ION MRI and LA-ICP-MS enables to study ION distribution and long-term fate, MRI iron quantification and validationof ION-based cell tracking in a specific, non-radioactive and quantitative manner.


57Fe-ION MRI supports research to study ION contrast agent biodistribution and long-term fate, to facilitate iron quantification andto validate MRI cell tracking studies.


SSQ12-05 CT Radiomic Features Predicting Epidermal Growth Factor Receptor Mutation Status In LungAdenocarcinoma


ParticipantsJun Zhang, PhD, Columbus, OH (Abstract Co-Author) Nothing to DiscloseBin Zhang, PhD, Cleveland, OH (Abstract Co-Author) Employee, Koninklijke Philips NVKatherine Binzel, PhD, Columbus, OH (Presenter) Nothing to DiscloseYu-lung Hsieh, PhD, Columbus , OH (Abstract Co-Author) Nothing to DiscloseRichard Moore, Columbus, OH (Abstract Co-Author) Nothing to DiscloseMichael T. Friel, BS, Columbus, OH (Abstract Co-Author) Nothing to DiscloseTaylor Porter, Columbus, OH (Abstract Co-Author) Nothing to DiscloseMichael V. Knopp, MD, PhD, Columbus, OH (Abstract Co-Author) Nothing to Disclose


[email protected]

PURPOSE

To introduce and evaluate low dose PET simulation using different approaches on the new generation solid state (SiPM) digitalphoton counting (DPC) Time-Of-Flight (TOF) PET/CT.


FDG PET/CT of uniformity phantom (~37MBq), NEMA Body phantom with 6 hot spheres (46MBq) and 82 tumors of oncology patients(460±47 MBq, 53±4 min p.i, 10-30 BMI) were imaged 90s/bed on a DPC TOF system (Vereos). Low dose PET (50% countsreduction) was generated based on listmode data using 3 simulation approaches: 1) Time-based (T): 45s/bed, 2) Space-based:Sparse-ring configurations with every other detector disabled in tangential (ST) and axial (SA), and 3) Order-based (O): everyother prompt event in order was extracted. Images were reconstructed in 3D-OSEM (low dose: 3i7s, full dose: 3i15s). Image qualitywas evaluated via blinded image review and quantitative assessment (lesion SUVmax, liver SUVmean, p value, Bland Altman Plots).

RESULTS

Visually, all lesions remained visible and clearly identifiable on all simulated half dose PET without compromised image quality. Imagenoise appeared visible at BMI >24, more on the half dose PET simulated by O approach than those by T and ST/SA approaches.Quantitatively, no significant SUVmax differences (-1±3%, -6±7%, -6±6% and -3±8%) were found (p=0.46, 0.33, 0.30 and 0.33)between any simulated half dose PET (T, ST, SA and O) and the full dose PET. Liver SUV was robust (-1±1% variances). BAPanalysis indicated good SUV correlation between half dose PET and full dose PET ([-0.07, -0.72, 0.58], [-0.36, -1.46, 0.73], [-0.43, -1.32, 0.46] and [-0.35, -1.81, 1.10] in [Bias, Lower LOA, Upper LOA] for T, ST, SA and O PET. Phantom PET showed moreconsistent results with less SUV variances compared to the clinical PET. More details on sensitivity, advantages and disadvantagesof the approaches will be presented.

CONCLUSION

The study demonstrated 3 approaches based on Time, Space and Order for low dose PET simulation. It indicated that theseapproaches are practicable to provide equivalent low dose PET simulation, and it is feasible to reduce PET dose by at least a factorof two from current standard of care (SOC) using the solid-state DPC PET.


It is challenging and also unethical to test low dose PET imaging in patients especially pediatric via sequential imaging protocols forcomparison, which necessitates simulation approaches to enable such.

ParticipantsGui-xue Liu, Shanghai , China (Presenter) Nothing to DiscloseXueqian Xie, MD, PhD, Groningen , Netherlands (Abstract Co-Author) Nothing to DiscloseZhihan Xu, MD, Shanghai, China (Abstract Co-Author) Nothing to DiscloseYing-Qian Ge, Shanghai, China (Abstract Co-Author) Nothing to DiscloseYaping Zhang, Shanghai, China (Abstract Co-Author) Nothing to DiscloseBei-Bei Jiang, Shanghai, China (Abstract Co-Author) Nothing to Disclose


[email protected]

PURPOSE

To evaluate the ability of CT radiomic features for predicting the epidermal growth factor receptor (EGFR) mutation status in Asianlung adenocarcinoma patients so as to choose the best targeted therapies.


The study was approved by the Institutional Review Committee and gave up informed consent. A total of 237 adenocarcinomapatients (115 males and 122 females; mean age of 62.30 ±9.57 years) who confirmed by pathological examination from July 2017 toDecember 2018 were involved in this study and undergone a chest CT (contrast-enhanced CT, Thickness 0.63mm) examinationbefore the operation. The data of EGFR gene expression, mutation sites, clinical features and CT imaging were collected andanalyzed retrospectively. Radiomics features were post-processed and extracted by Radiomics software, implemented in a clientserver application of the manufacturer (syngoVia, Research Frontier, Siemens Healthcare, Germany). A total of 849 CT featureswere extracted from the volume of each tumor. After the feature selection by univariate analysis, multivariate logistic regressionanalysis was used to build the classifiers to predict the mutation status of EGFR.

SSQ12-06 Non-Invasive, Macrophage-Specific Spectral Photon Counting CT K-Edge Imaging in AtherosclerosisUsing PEGylated Gold Nanoparticles


SSQ12-07 Prognostic Value of Radiomic Features from 18F-FDG PET/CT in Patients with Oral Cavity SquamousCell Carcinoma


RESULTS

Univariate analysis showed a statistically significant correlation between patient gender and EGFR mutation with p = 0.003. 72 of849 imaging radiomic features were proved that had statistically associated with EGFR mutation (p<0.05). The top 10 most relevantfeatures were involved to establish the logistic regression models. In model selection, two and eight features were applied to buildclassifier by the min-BIC and min-AIC criteria respectively. The performances of logistic regression classifiers with radiomic featuresobtained the AUC of 0.81 and 0.75 with min-AIC and min-BIC selected respectively. Their AUCs were improved to 0.83 and 0.75 byadding patient gender into the model establishment. The sensitivity and specificity were 77% and 81% at the best diagnosticdecision point.

CONCLUSION

CT imaging radiomic features of lung adenocarcinoma combined with clinical variables showed better performance on predicting themutation status of EGRF. CT imaging radiomic features might have the potential to be the biomarker for identifying EGRF mutations.


Radiomics could not only investigate the genetic mutations among tumors but also show the diagnostic value and have thepotential to be a diagnostic tool in the future.

ParticipantsSalim Si-Mohamed, Bron, France (Abstract Co-Author) Nothing to DiscloseDavid P. Cormode, DPhil, MS, Philadelphia, PA (Abstract Co-Author) Research Grant, Koninklijke Philips NV; Stockholder, PolyAurum;Stockholder, Daimroc ImagingMonica Sigovan, PhD, San Francisco, CA (Abstract Co-Author) Nothing to DiscloseMarine Breuilly, Lyon, France (Abstract Co-Author) Nothing to DisclosePratap Naha, PhD, Philadelphia, PA (Abstract Co-Author) Nothing to DiscloseLara Chalabreysse, Lyon, France (Abstract Co-Author) Nothing to DisclosePhilippe Coulon, PhD, Dourdan, France (Abstract Co-Author) Nothing to DiscloseHeiner Daerr, Hambrg, Germany (Abstract Co-Author) Nothing to DiscloseYoad Yagil, PhD, Haifa, Israel (Abstract Co-Author) Employee, Koninklijke Philips NVLoic Boussel, MD, Lyon, France (Abstract Co-Author) Nothing to DisclosePhilippe C. Douek, MD, PhD, Lyon, France (Presenter) Nothing to Disclose


[email protected]

PURPOSE

To detect and quantify the macrophages component within the atherosclerotic plaques using a pegylated gold nanoparticles and aspectral photon-counting computed tomography (SPCCT) via K-edge imaging, in comparison to histological, transmission electronmicroscopy analysis and quantitative ICP mass spectrometry.


In vivo imaging was performed on 7 atherosclerotic and 4 non-atherosclerotic NZW rabbits (control) using thiol-pegylated goldnanoparticles. Imaging was performed with a prototype SPCCT system over two days. Quantitative analysis was based on theattenuation (HU) and concentrations of gold measured on gold K-edge images within the aortic parietal wall. Transmission electronmicroscopy (TEM) on 8 following slices to the ones used for histology on atherosclerotic rabbits was performed to confirm themacrophage uptake of gold nanoparticles.

RESULTS

SPCCT images depicted a thickened aorta with few calcifications before injection. Conventional and K-edge images depictedenhancement within the arterial lumen after injection corresponding to arterial peak and blood pool imaging effect. Atheroscleroticplaque enhancement was observable at day 1 and 2, appearing as a well delimited enhanced plaque, supported by a thickenedparietal wall and some calcifications.Only the K-edge images allow of the distinction of plaque enhancement within calcifications.TEM images of rabbit aorta sections confirmed the localization in high number of gold nanoparticles in macrophages.

CONCLUSION

We show the feasibility of noninvasive specific detection and quantification of macrophages in atherosclerotic plaques of rabbitsusing the K-edge capability of SPCCT and intravenous injection of pegylated gold nanoparticles.


Noninvasive specific detection and quantification of macrophages in atherosclerotic plaques using spectral photon-counting CT andintravenous injection of pegylated gold nanoparticles may be helpful for diagnosis and prognosis in atherosclerosis, in particular forcoronary imaging.

ParticipantsYasser Abdelhafez, MD, Sacramento, CA (Presenter) Nothing to DiscloseYimeng Dou, BS, Davis, CA (Abstract Co-Author) Nothing to DiscloseTzu-Chen Yen, MD, PHD, Taoyuan, Taiwan (Abstract Co-Author) Nothing to DiscloseChun-Ta Liao, Tayouan, Taiwan (Abstract Co-Author) Nothing to Disclose

SSQ12-08 High Definition Image Reconstruction: Enhancing PET Quantification as Enabled by Digital PhotonCounting PET/CT


Abhijit J. Chaudhari, PhD, Sacramento, CA (Abstract Co-Author) Nothing to Disclose

PURPOSE

To evaluate the prognostic value of radiomic features extracted from pre-operative 18F-FDG PET/CT in patients with advancedstage oral cavity squamous cell carcinoma (OCSCC)


The study retrospectively included 113 patients with advanced stage OCSCC (pathologic TNM stage III=28, IV=85; 107 males, 6females; median age 49 years, range: 29-89). All patients had biopsy-proven SCC of oral cavity, locally- or loco-regionallyadvanced disease with no distant metastasis (M0), and staging 18F-FDG PET/CT scan. Patients were treated with surgicalresection of the primary tumor followed by adjuvant chemo(radio)therapy. The maximum pathologic axial tumor size was 33.5±16.8mm. Primary tumor from PET images was segmented using absolute isocontour threshold of 40% of the maximum standard uptakevalue (SUV). Using TextIriX, a texture analysis plugin developed for OsiriX by our group, a total of 78 radiomic features (includingshape, first order and texture features) were extracted. SUVs within the segmented volume were normalized between the minimumand maximum values, then discretized into 64-bins to construct the grey-level matrices. No spatial resampling was used. ROCcurves of the extracted features were plotted against disease-specific survival (DSS) status. All patients had a follow-up of 5-years or till death.

RESULTS

Fifty-two patients died of cancer (5-year DSS=51.6%). The following radiomic features were associated with DSS (run entropy,zone entropy, entropy, dependence entropy, dependence non-uniformity, size zone non-uniformity, run-length non-uniformity),with AUC ranging from 0.637-0.661 (p < 0.01). Using backward Cox hazard model with 1000-samples bootstrapping, only runentropy (randomness in the distribution of run lengths and gray levels) was independently associated with DSS (hazards ratio=2.71,95% confidence interval=1.5-5, p=0.001). When dichotomizing all patients by median value of run entropy (value=5.2), patientswith entropy <= median had 5-year-DSS of 64.5% with mean survival time of 72.6 months compared to 5-year DSS of 38.5% andmean survival time of 42.4 months for patients with high entropy (p=0.003).

CONCLUSION

Tumor run entropy from 18F-FDG PET/CT was significantly and independently associated with disease-specific survival in patientswith OCSCC.


Radiomic features extracted from 18F-FDG-PET/CT are associated with prognosis in patients with oral cavity cancer.

ParticipantsKatherine Binzel, PhD, Columbus, OH (Presenter) Nothing to DiscloseTaylor Porter, Columbus, OH (Abstract Co-Author) Nothing to DiscloseRichard Moore, Columbus, OH (Abstract Co-Author) Nothing to DiscloseMichael T. Friel, BS, Columbus, OH (Abstract Co-Author) Nothing to DiscloseYu-lung Hsieh, PhD, Columbus , OH (Abstract Co-Author) Nothing to DiscloseJun Zhang, PhD, Columbus, OH (Abstract Co-Author) Nothing to DiscloseMichael V. Knopp, MD, PhD, Columbus, OH (Abstract Co-Author) Nothing to Disclose


[email protected]

PURPOSE

Digital photon counting PET/CT enables more sensitive event detection and localization, leading to an increase in count density inthe image data allowing image reconstruction with a larger matrix size resulting in smaller voxel volumes. We evaluated thequantitative impact of higher definition reconstruction on clinical data acquired on a next-generation digital photon counting PET/CTsystem.


80 clinical patients were imaged for 90 seconds per bed position on a solid state digital photon counting PET/CT system (PhilipsVereos, dPET) following injection of 13 mCi 18F-FDG. Standard definition (SD) reconstruction used a 4x4x4 mm3 isometric voxelvolume, 144x144 matrix. Secondary reconstructions were completed using a 2x2x2 mm3 voxel volume, 288x288 matrix (highdefinition, HD) protocol, and a 1x1x1 mm3 voxel volume, 576x576 matrix (ultra-high definition, UHD) protocol. Using the SD imagesas reference, target tumor lesions and physiologic uptake were assessed by SUVmax and SUVmean, respectively. The percentdifference from SD reconstruction measurements was calculated.

RESULTS

Quantification was significantly (p<0.05) improved by the use of larger reconstruction matrices. In background tissues, the averageSUVmean increased 2.7% from SD values for the HD images and 4.3% for the UHD images. In target lesions the SUVmax increasedan average of 24.9% and 57.9% for HD and UHD reconstructions. These improvements are consistent with the improved recoverycoefficients seen in phantom data. The change in SUVmax of target tumor lesions was related to the tumor volume, with lesionsless than 5cm3 having greater increases in SUVmax than lesions which were larger or more homogeneous.

CONCLUSION

High definition image reconstruction improves quantification of PET radiotracer activity. The reduction in partial volume effectscreated by utilizing smaller voxel sizes is enabled by the improved count senstivity and substantially faster time of flight timingresolution of the digital photon counting PET/CT platform.

SSQ12-09 Improving 18F-FMISO Hypoxia Target Map with EPRI and DCE-MRI

Thursday, Dec. 5 11:50AM - 12:00PM Room: S501ABC


Next-generation digital photon counting PET/CT technology enables the use of larger reconstruction matrices due to improvementsin spatial resolution and annihilation event localization.

ParticipantsInna Gertsenshteyn, BA, Chicago, IL (Presenter) Nothing to DiscloseBoris Epel, PhD, Chicago, IL (Abstract Co-Author) Patent holder, 9,392, 957 ; Member, O2MLara Leoni, PhD, Chicago, IL (Abstract Co-Author) Nothing to DiscloseEugene Barth, Chicago, IL (Abstract Co-Author) Nothing to DiscloseXiaobing Fan, PhD, Chicago, IL (Abstract Co-Author) Nothing to DiscloseMarta A. Zamora, BS, Chicago, IL (Abstract Co-Author) Nothing to DiscloseErica Markiewicz, BA, Chicago, IL (Abstract Co-Author) Nothing to DiscloseRichard Freifelder, PhD, Chicago, IL (Abstract Co-Author) Nothing to DiscloseMohammed Bhuiyan, PhD, Chicago, IL (Abstract Co-Author) Nothing to DiscloseAnna Kucharski, PhD, Chicago, IL (Abstract Co-Author) Nothing to DiscloseDarwin Bodero, BA, Chicago, IL (Abstract Co-Author) Nothing to DiscloseHsiu-Ming Tsai, PhD, Chicago, IL (Abstract Co-Author) Nothing to DiscloseGregory S. Karczmar, PhD, Crete, IL (Abstract Co-Author) Nothing to DiscloseChien-Min Kao, PhD, Chicago, IL (Abstract Co-Author) Stockholder, Walgreens Boots Alliance, IncChin-Tu Chen, PhD, Chicago, IL (Abstract Co-Author) Board Member, BioMed Global Board Member, EVO Worldwide, Inc BoardMember, AEPX Board Member, EnDepth Vision Systems, LLC Research Grant, DxRay, Inc Advisor, RefleXion Medical Inc Shareholder,EDDA Technology, IncHoward J. Halpern, MD, PhD, Chicago, IL (Abstract Co-Author) Patent holder, 8,664,955 ; Patent holder, 9,392,957 ; Member, O2MTechnologies

PURPOSE

Electron Paramagnetic Resonance (EPR) pO2 images provide a radiobiologically validated standard to accurately identify hypoxiawithin tumors. Using EPR pO2 images as ground truth, we show the modification of PET-18F-MISO images using dynamic contrastenhanced (DCE)-MRI to better predict true hypoxia as defined by EPR in preclinical models for the eventual translation of thisapplication to clinical human imaging.


We used 6 MCa4 and SCC7 tumor mouse models grown in the leg in the range of 250-400 mm^3. Under minimal anesthesia, eachmouse leg was set in a soft vinylpolysiloxane cast and imaged in EPR using trityl as the oxygen spin probe, followed by a T2 andDCE-MRI using gadolinium as the contrast agent, then a PET/CT scan using FMISO as the radiotracer to target hypoxia. Based onthe Tofts model, ktrans and kep maps were obtained from DCE-MRI, as well as the Relative Signal Increase (RSI) of contrast. Datafrom all modalities were registered. We modeled radiotracer retention as the logistic function of pO2 to map the quantitative EPRpO2 image to PET-FMISO Tumor:Muscle ratio (TMR) images, so that its sigmoidal point of inflection was at the threshold ofretention. Then a linear combination of the PET and DCE-MRI data was mapped to the logistic[pO2] data using the least squaresmethod, and that combination of PET-DCE-MRI data was finally mapped back to EPR pO2 torr units by applying an inverted logisticfunction as a check. The Dice coefficient between EPR pO2 < 15 torr and PET or modified PET > 1.4 TMR was used as a metric ofthe effectiveness of mapping.

RESULTS

On average, the Dice coefficient before and after implementing our mapping method increased by 32% to define hypoxic regionswithin the tumor. We anticipate that a more sophisticated combination including a nonlinear combination of PET and MRI willimprove Dice coefficient overlap of PET-FMISO and EPR pO2 image-defined hypoxia.

CONCLUSION

The improvement of overlap between our reference standard of hypoxia definition by EPR with mapped PET-DCE-MRI whencompared to PET-FMISO alone shows that using solely PET-FMISO to define hypoxia is insufficient.


Our mapping method to improve the accuracy of hypoxia definition using clinically accepted imaging methods can improveradiotherapy outcomes for tumor cure, and show another clinical advantage of PET-MRI imaging.


MI213-SD-THA1

Basic Research on AQP9-MR Molecular Imaging of HCC: The Differential Expression of AQP9 in HCCTumor Tissues

Station #1

MI217-SD-THA2

Radiomics Features as a Predictor of Survival in Patients Affected by Pulmonary Metastatic Melanoma

Station #2

MIS-THA

Molecular Imaging Thursday Poster Discussions

Thursday, Dec. 5 12:15PM - 12:45PM Room: MI Community, Learning Center

MI


ParticipantsDima A. Hammoud, MD, Bethesda, MD (Moderator) Nothing to Disclose

Sub-Events

ParticipantsYani Kuang, BMedSc, Taizhou, China (Presenter) Nothing to DiscloseWenbin Ji, Taizhou , China (Abstract Co-Author) Nothing to Disclose


[email protected]

PURPOSE

To investigate the expression differences of AQP9 between HCC tissues, tumor surrounding cells and liver normal cells, and to verifythe feasibility of AQP9 as a molecular imaging target for HCC.


30 patients with liver cancer who were hospitalized in our hospital from April 2009 to September 2015 were prospectively included,and their pathological specimens were collected after surgery. After the labeling of all samples, the specific antigen was detectedand the target protein was extracted. The genetic sequence of the target protein was amplified and detected by fluorescencequantitative PCR, and the Ct value was determined. The initial copy number of AQP9 in each sample was obtained by using thestandard curve. Statistical analysis was done by SPSS18.0 software to compare the differences of each value between groups andanalyze correlation of relative factors of groups. P<0.05 was considered statistically significant.

RESULTS

There were 26 males and 4 females in the 30 cases, with an average age of 57.6 years. There were 26 cases of HCC, 3 cases ofcholangiocarcinoma and 1 case of partial cholangiocarcinoma. There was no significant difference between the expression level ofAQP9 in para-tumor tissues and that of normal hepatocytes (1.01 ±0.01 vs. 1.01±0.76, q= 0.04656,P=0.9984).The expression ofAQP9 in tumor tissues was significantly lower than that in normal hepatocytes, with statistically significant differences (1.01 ±0.01vs. 0.36± 0.36, q=4.122, P=0.0003).

CONCLUSION

AQP9 is differentially expressed in HCC tissues, para-tumor tissues and normal liver tissues, and the expression of AQP9 in HCCtissues is significantly lower than that in para-tumor tissues and normal liver tissues. AQP9 can be used as a target for MRmolecular imaging of HCC.


Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Aquaporins (AQPs) refer to the membrane intrinsicproteins that can selectively and efficiently transport water molecules. One scan of AQP MR imaging can obtain the information oftissue capillary blood perfusion, intercellular water molecule diffusion, and changes of AQP expression on the cell membrane.Specific liver AQP9-MR molecular imaging can be used for the diagnosis of HCC, the evaluation of therapeutic efficacy and theestablishment of a database for high-throughput data analysis, so as to find a new breakthrough for the diagnosis and treatment ofHCC.

ParticipantsLuca Baffoni, MD, Padova, Italy (Presenter) Nothing to DiscloseAndrea Bettinelli, Padua, Italy (Abstract Co-Author) Nothing to DiscloseGiulia Fichera, MD, Padova, Italy (Abstract Co-Author) Nothing to DiscloseLaura Bonanno, Padova, Italy (Abstract Co-Author) Nothing to DiscloseFrancesco Morra, MD, Padua, Italy (Abstract Co-Author) Nothing to DiscloseAlice Pittaro, Padova, Italy (Abstract Co-Author) Nothing to DiscloseLuisa Piccin, Padova , Italy (Abstract Co-Author) Nothing to DiscloseChiara Giraudo, MD,PhD, Padova, Italy (Abstract Co-Author) Nothing to DiscloseVanna Chiarion Sileni, Padua, Italy (Abstract Co-Author) Nothing to DiscloseEmilio Quaia, MD, Padova, Italy (Abstract Co-Author) Nothing to DiscloseMarta Paiusco, Padua, Italy (Abstract Co-Author) Nothing to Disclose


[email protected]

PURPOSE

Radiomics is an innovative field of radiology, allowing quantitative data extraction from radiological images which can be applied as asurvival predictor especially in the oncological field. The aim of our study was to determine if radiomic features of lung metastasesin patients affected by melanoma could predict the overall survival.


Patients with stage IV melanoma affected by lung metastasis, who underwent a contrast enhanced CT scan prior the beginning ofthe immunotherapy with anti programming cell-death 1 (PD-1) were included. The patients were subdivided in two groups,according to the overall survival (i.e., dead at the time of the study, D+, alive at the time of the study, D-). Three radiologistsexpert in oncological imaging, performed a blinded and independent segmentation, drawing a region of interest (ROI) along themargins of the biggest metastatic lesion of the lung using a software. 505 radiomic features were extracted using IBEX softwareand analyzed with Matlab and R-software. The feature stability using intraclass correlation coefficient (ICC) for feature reductionretaining was evaluated. A Wilcoxon based method were obtained and then included in the COX proportional hazard ratio model.Finally a survival curve with Kaplan Meyer method was performed (log-rank, p-value<0.05).

RESULTS

Overall 25 patients with lung metastasis of melanoma, six dead at the time of the analysis, matched the inclusion criteria (9females, mean age 62,22 ± 12,19 yrs). One hundred and forty-five out of the 505 investigated features showed stability;four ofthese (GLDZM, Zone Distance Variance; IVH, Area Under IVH Curve; GLDZM, Large Distance Emphasis; GLDZM, Large Distance HighGLE Emphasis) demonstrated a statistically significant difference between survivors and not-survivors (p=0.01).

CONCLUSION

Radiomic features seem to be markers of survival in patients with lung metastasis of melanoma.


Radiomic features could become predictor of survival in patients affected by metastatic lung melanoma before immunotherapy witha strong impact on the therapeutic approach.


MI214-SD-THB1

Fe3+@PolyDOPA-b-Polysarcosine, a T1-Weighted MRI Contrast Agent via Controlled NTAPolymerization

Station #1

MI218-SD-THB2

CT Radiomic Features Predicting Epidermal Growth Factor Receptor Mutation Status of Exon 19 andExon 21 in Lung Adenocarcinoma

Station #2

MIS-THB

Molecular Imaging Thursday Poster Discussions

Thursday, Dec. 5 12:45PM - 1:15PM Room: MI Community, Learning Center

MI



ParticipantsDima A. Hammoud, MD, Bethesda, MD (Moderator) Nothing to Disclose

Sub-Events

ParticipantsXue Dong, Hangzhou, China (Presenter) Nothing to DiscloseJiayu Cen, Hangzhou, China (Abstract Co-Author) Nothing to DiscloseJingfeng Luo JR, PhD, Hangzhou , China (Abstract Co-Author) Nothing to DiscloseXiuyu Guo, Xiamen, China (Abstract Co-Author) Nothing to DiscloseYuedong Miao, Hangzhou , China (Abstract Co-Author) Nothing to DiscloseJun Ling, Hangzhou , China (Abstract Co-Author) Nothing to DiscloseJihong Sun, MD, PhD, Hangzhou, China (Abstract Co-Author) Nothing to Disclose


[email protected]

PURPOSE

To assess the applicability of novel PDOPA-b-polysarcosine nanoparticles (PDOPA-b-PSar) as high-relaxivity T1 magnetic resonanceimaging (MRI) contrast agent for tumor diagnosis.


PDOPA-b-PSar were synthesized via the sequential copolymerization of sarcosine-N-thiocarboxyanhydride (Sar-NTA) and 3,4-dihydroxy-L-phenylalanine NTA (DOPA-NTA) containing unprotected phenolic hydroxyl groups. Fe3+@PDOPA-b-PSar micellarnanoparticles were prepared on the basis of strong chelation between iron (III) cations and catechol groups. T1 relaxivity (r1)measurements were performed at 3.0-T MR field strengths. Cell proliferation and apoptosis were evaluated in vitro. T1-weighteddynamic contrast-enhanced MRI was performed in vivo in tumor-bearing mice that were intravenously injected with PDOPA-b-PSar.

RESULTS

The longitudinal relaxivity of Fe3+@PDOPA10-b- PSar50 is higher than that of commercial Gd3+-based compounds (r1 =5.6 mM-1s-1). In vivo MRI of Fe3+@polyDOPA-b-polysarcosine-treated tumor-bearing mice revealed strong signal enhancement of thetumor area because of enhanced permeability and retention. In vivo analysis also indicated that the maximum contrast-to-noiseratio of the tumors in the T1-weighted imaging mode increased up to 6.46±1.3,and reduced to 3.45±0.44,4h and 24h after theinjection of Fe3+@PDOPA-b-PSar ,respectively. Cytotoxicity assay showed that Fe3+@PDOPA-b- PSar had relatively lowcytotoxicity and high biocompatibility in NIH 3T3 cells.

CONCLUSION

Fe3+-polypept(o)ides nanoparticles are novel, Gd-free, nontoxic T1-weighted MRI contrast agents with the potential to replacetraditional Gd3+ compounds. These unique properties of Fe3+@PDOPA-b-PSar make them highly efficient for tumor-targeted MRI invivo, possibly improving tumor diagnosis and enabling more accurate tumor therapy.


Fe3+-polypept(o)ides nanoparticles may replace traditional Gd3+ compounds as a T1-weighted MRI contrast agents to improvetumor diagnosis and accurate tumor therapy.

ParticipantsGui-xue Liu, Shanghai , China (Presenter) Nothing to DiscloseXueqian Xie, MD, PhD, Groningen , Netherlands (Abstract Co-Author) Nothing to DiscloseZhihan Xu, MD, Shanghai, China (Abstract Co-Author) Nothing to DiscloseYing-Qian Ge, Shanghai, China (Abstract Co-Author) Nothing to DiscloseYaping Zhang, Shanghai, China (Abstract Co-Author) Nothing to DiscloseBei-Bei Jiang, Shanghai, China (Abstract Co-Author) Nothing to Disclose

mailto:Fe3+@PDOPA10-b- PSar

mailto:Fe3+@PDOPA10-b-PSar50

mailto:Fe3+@polyDOPA-b-polysarcosine-treated

mailto:Fe3+@PDOPA-b- PSar


[email protected]

PURPOSE

To assess the CT radiomic features in predicting the exon 19 deletion(Del19) and exon 21 (L858R) mutations in lungadenocarcinoma patients for choosing the best targeted therapies.


The study was approved by the Institutional Review Committee and gave up informed consent. 148 lung adenocarcinoma patients(61 males and 87 females; mean age 61.5 ±9.57 years) were involved in this study, which were confirmed by pathologicalexamination from July 2017 to December 2018. All patients had undergone chest CT (contrast-enhanced CT, thickness 0.63mm)examination before operation. The data of EGFR gene mutation sites, clinical features and CT imaging were collected and analyzedretrospectively. Radiomics software which implemented in a client server application of the manufacturer (syngoVia, ResearchFrontier, Siemens Healthcare, Germany) was used to post-process and extract radiomic features. For each tumor, 848 radiomicfeatures were extracted. Multivariate logistic regression analysis was used to establish the classifiers to predict the mutation typeexon Del19 and L858R with the selected features, which were filtered by univariate analysis.

RESULTS

Univariate analysis showed a statistically significant correlation between patient age and exon 21 (L858R) mutation with p = 0.039.31 of 848 imaging radiomic features were proved that have statistically associations with exon 21 (L858R) (p<0.05). The top 10most relevant features were involved to establish the logistic regression models. In model selection, two and eight features wereapplied to build classifiers by the min-BIC and min-AIC criteria respectively. The performances of logistic regression classifiers withradiomic features obtained the area under curve (AUC) of 0.78 and 0.75 with min-AIC and min-BIC selected respectively. The AUCswere improved to 0.79 and 0.72 by adding patient age into the model establishment. The sensitivity and specificity were 73.5% and72% at the best diagnostic decision point.

CONCLUSION

CT radiomic features of lung adenocarcinoma combined with clinical variables could better predict the mutation types of EGRF gene.Radiological characteristics might have potential alternative biomarkers for differentiating the exon Del19 and 21 (L858R) mutations.


Radiomic features had potential to use noninvasive method to identify genetic mutation types, which leaded to the betterindividualized treatments for patients.


SPSH54A Imaging of Acute TBI

SPSH54B PET Tracers to Assess TBI and CTE

SPSH54C Advanced MRI Techniques for TBI Research

SPSH54

Hot Topic Session: Imaging of Traumatic Brain Injury-Present and Future

Thursday, Dec. 5 3:00PM - 4:00PM Room: E451A

ER MI NR


ParticipantsDonna J. Cross, PhD, Salt Lake City, UT (Moderator) Nothing to Disclose

LEARNING OBJECTIVES

1) Describe new and universal approaches for the visual examination of acute brain injury. 2) Examine novel approaches for theassessment of traumatic brain injury. 3) Describe methods under development to assess traumatic brain injury-relatedneurodegenerative disorders.

ABSTRACT

This session will highlight molecular imaging of traumatic brain injuries from current clinical work up of acute injury to tracerdevelopment for the assessment of chronic brain injury such as Chronic Traumatic Encephalopathy. Topics will include new PETtracers, MRI methodologies and quantitative analyses currently used in research.

Sub-Events

ParticipantsYoshimi Anzai, MD, Salt Lake City, UT (Presenter) Nothing to Disclose


[email protected]

ParticipantsGerard N. Bischof, PhD, Cologne, Germany (Presenter) Nothing to Disclose

ParticipantsPratik Mukherjee, MD, PhD, San Francisco, CA (Presenter) Research Grant, General Electric Company; Medical Adivisory Board,General Electric Company; Patent Pending USPTO No. 62/269,778


RC817A Thyroid Cancer: 131-I Na Therapy

RC817B Phaeochromocytomas and Paragangliomas: 131-I MIBG Therapy

RC817C Neuroendocrine Tumors: 177Lu-DOTATATE Therapy

RC817D Prostate Cancer: 177Lu-PSMA Therapy

RC817

Emerging Technology: Theranosis-Molecularly Targeted Therapies 2019

Friday, Dec. 6 8:30AM - 10:00AM Room: E260

MI NM



ParticipantsRathan M. Subramaniam, MD,PhD, Dunedin, New Zealand (Moderator) Nothing to Disclose


[email protected]

LEARNING OBJECTIVES

1) To review the established and emerging molecularly targeted radionuclide therapies for human solid tumors.

Sub-Events

ParticipantsArif Sheikh, MD, New York, NY (Presenter) Nothing to Disclose


[email protected]

LEARNING OBJECTIVES

1. To review the basic approaches of radioiodine therapy in thyroid cancer management 2. To evaluate the integration ofradioiodine imaging and therapy in thyroid cancer 3. Understanding radioiodine therapy as the general model for theranostics

ParticipantsLilja B. Solnes, MD, Baltimore, MD (Presenter) Advisory Board, Progenics Pharmaceuticals, Inc

ParticipantsRathan M. Subramaniam, MD,PhD, Dunedin, New Zealand (Presenter) Nothing to Disclose


[email protected]

LEARNING OBJECTIVES

1) To learn the indications and patient selections for 177Lu DOTATATE therapy. 2) To review the 177Lu DOTATATE therapyprocedures, toxicity monitoring and patient care follow-up. 3) To review therapy response methods for 177Lu DOTATATEtreatments.

ParticipantsAyse T. Karagulle Kendi, MD, Rochester, MN (Presenter) Investigator, Endocyte, Inc


[email protected]

LEARNING OBJECTIVES

1) Brief review of clinical background. 2) Discuss basic principles of Lu-PSMA therapy. 3) Describe therapy methods. 4) Explain sideeffects. 5) Review clinical impact/outcomes of Lu-PSMA therapy.


Documents

Molecular Imaging - archive.rsna.org