emerged as one of the most promising clinical tools for de-tection of breast cancer and delineation of its anatomic ex-tent. NMR spectroscopy in vivo of cellular metabolism intumors may further augment imaging diagnostic methods. Toencourage the promise of magnetic resonance based diagnos-tics, the NCI has issued at least a dozen program announce-ments over the past decade specifically requesting grant ap-plications for MR based investigation of breast cancer. Basedon preliminary human breast exams performed at 4T, and onadditional human imaging experience at 4T and 7T, we pos-tulate that the most sensitive and highly specific detection ofbreast cancer by MR imaging and spectroscopy methods willrequire the use of high sensitivity breast coil receivers to-gether with high homogeneity chest coil transmitters, at thehighest magnetic fields available. We intend to investigatethis hypothetical assertion by developing a single tuned andmultinuclear chest coils paired with phased array receivers tomake dual breast imaging and spectroscopy possible at 4Tand 7T. Currently there are no such capabilities for highfield breast studies. Cancer detection in breasts will be im-proved with this new high field technology by the increasedsignal-to-noise, spectral resolution and fat suppression it fa-cilitates. Specificity will be improved and scan time reducedby imaging both breasts simultaneously to facilitate anatomicand metabolic comparison between healthy and cancerousbreasts for an individual. The chest coils will be activelyswitched between transmit and receive modes, and will beactively decoupled from the independent breast receivercoils. This new RF technology will be tested on forty breastcancer patients by the breast imaging and spectroscopymethods proposed. Improvements in data quality and diag-nostics results will be evaluated to prove the new technologyand methods developed.

Thesaurus Terms: biomedical equipment development,breast neoplasm/cancer diagnosis, magnetic resonance imag-ing, nuclear magnetic resonance spectroscopy biologicalmodel, magnetic field, neoplasm/cancer classification/staging,neoplasm/cancer invasiveness, noninvasive diagnosis, radio-wave radiation bioimaging/biomedical imaging, clinical re-search, female, human subject, patient oriented research,swine, women’s health

Institution: University Of Minnesota Twin CitiesSuite 450 McNamara Alumni CenterMinneapolis, MN 554552070

Fiscal Year: 2002Department: RadiologyProject Start: 01-Jun-2002Project End: 31-May-2005ICD: National Cancer InstituteIRG: ZCA1

BLOOD POOL CONTRAST AGENTS FORCT AND MRI

Grant Number: 5R01CA082335-03PI Name: Vera, David R.

Abstract: Description (Adapted from Applicant’s Abstract):The investigators propose a project in which they will syn-thesize and test a new class of blood pool agents for com-puted tomography (CT) and magnetic resonance (MR) imag-ing. The proposal includes preliminary data demonstratingthat the proposed agent enhanced CT visualization of hepaticvessels and provided MR detection of tumor vasculature foran extended period of time. The proposed agent is based ona molecular backbone of dextran to which multiple reporterunits of Gd-DTPA are covalently attached. Using dextran asa molecular backbone offers many advantages. First, the factthat the agent is not a particle should increase biologicalsafety. Second, dextran is available in a variety of molecularweights; this will make it possible to optimize the agent’sblood residence time and tumor permeability. Third, dextranis composed of repeating glucose units, each of which hasthree potential attachment sites fore each Gd-DOTA-reporterunit. This property will permit optimization of the agent.Fourth, the extensive human use experience with dextranincreases the probability that the agent will be safe. The ob-jective is to develop a new class of imaging agent with theappropriate attributes for detection of tumors and other tissuepathology resulting from abnormal tissue vascularity. Theseattributes include adequate blood enhancement, favorableresidence time within the blood, chemical stability in vitroand in vivo, and high plasma specificity. The project has fivespecific aims. 1) The first is a level of enhancement that willgive hepatic vessels a twofold greater signal than hepatictissue. After preliminary CT and MR imaging studies in rab-bits during the Years-01 and B02, a crossover design will beused to compare the CT and MR imaging properties of thenew, optimized agent with those of standard contrast media.2) Plasma half-time of one hour will be achieved by selec-tion of dextran size and reporter density. Preliminary dataindicate that a dextran backbone with a molecular weight of10 g/mole and a reporter density of two Gd-DOTA units perglucose should accomplish this goal. Plasma clearance willbe measured using Gd-153- and C-14-labeled agents. 3) Toverify the stability of the Gd-complex; the investigators willtest in vitro stability and dissociation inertia. 4) The investi-gators will measure the agent’s biodistribution using radiola-beled components (Gd-153, C-14-DOTA, C-14-methyl-dex-tran, and a S-35 label for the Dota-to-dextran leash). 5. Dur-ing the 4-year project the investigators will scale-up thesynthesis and maximize reporter densities. At the completionof this project, the necessary information will be available todetermine the clinical potential as a new blood pool agentfor CT and MR imaging. This agent is expected to provideincreased sensitivity for cancer detection and staging, greater

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imaging flexibility, and increased patient comfort. Addition-ally, this structure will serve as a neural carrier of for futureclass of nonparticulate receptor-binding CT and MR contrastmedia.

Thesaurus Terms: cardiovascular imaging/visualization,computed axial tomography, contrast media, drug design/synthesis/production, magnetic resonance imaging, neoplasm/cancer blood supply blood drug, dextran, diethylenetriamine-pentaacetate, gadolinium bioimaging/biomedical imaging

Institution: University Of California San Diego9500 Gilman Dr, Dept. 0934La Jolla, CA 92093

Fiscal Year: 2002Department: RadiologyProject Start: 01-Apr-2000Project End: 31-Mar-2004ICD: National Cancer InstituteIRG: ZRG1

THE BIOLOGY OF LUNG CANCER– FDGAND FLUOROTHYMIDINE PET

Grant Number: 5R01CA080907-03PI Name: Vesselle, Hubert J.

Abstract: The objective of the proposed studies is to investi-gate quantitative [F-18]fluorodeoxyglucose (FDG) PositronEmission Tomography (PET) as a measure of non-small celllung cancer (NSCLC) aggressiveness in vivo (i.e. grading)and to make comparisons with patients’ outcomes and withspecimen-derived measures of cellular proliferation previ-ously shown to predict poor outcome (S-phase fraction,Ki-67 index). We postulate that, in clinically resectableNSCLC patients, pre-operative FDG PET will show that tu-mors with higher FDG uptake: (a) will recur sooner aftersurgical resection than same stage tumors with low uptake;(b) are more likely to have mediastinal or distal metastaticdisease than tumors of the same clinical stage but low up-take; (c) have higher S-phase fraction of Ki-67 scores intheir resected specimen. The specific aims of the proposalare: (1) Perform whole-body pre- operative FDG PET imag-ing and correlate FDG uptake in primary NSCLC with out-come. FDG uptake will be quantified by the following meth-ods that will be compared. Standardized Uptake Value(SUV) and SKM-FDGMR (FDG Metabolic Rate determinedby a Simplified Kinetic Method). (2) Perform whole-bodypre-operative FDG PET imaging and correlate FDG uptake(quantified as SUV and SKM-FDGMR) in primary NSCLCwith disease extent as demonstrated by PET and surgicalstaging. (3) Correlate pre-operative FDG uptake in primaryNSCLC with markers of cellular proliferation measured fromthe resected specimen and previously shown to predict pooroutcome. Outcome will be measured by recurrence-free sur-

vival, time-to recurrence and survival. In summary, by study-ing NSCLC patients pre-operatively, prior to any form ofchemotherapy or radiotherapy, we will gain valuable infor-mation about the biology of lung cancer, the leading causeof cancer death in the United States. By performing a bio-logic grading of resectable NSCLC with FDG PET, we willpredict which patients will have a worse outcome. This in-formation will allow individualized therapy.

Thesaurus Terms: deoxyglucose, lung imaging/visualiza-tion/scanning, nonsmall cell lung cancer, positron emissiontomography, prognosis DNA replication, biomarker, cell pro-liferation, glucose metabolism, metastasis, neoplasm/cancerclassification/staging, neoplasm/cancer relapse/recurrence,outcomes research, postoperative state, preoperative state,radiation dosage, tumor progression bioimaging/biomedicalimaging, clinical research, flow cytometry, human subject,immunocytochemistry

Institution: University Of WashingtonSeattle, WA 98195

Fiscal Year: 2002Department: RadiologyProject Start: 12-Jan-2000Project End: 31-Dec-2004ICD: National Cancer InstituteIRG: RNM

METABOLIC IMAGING OF THEPROSTATE USING 3D MRSI

Grant Number: 5R01CA059897-10PI Name: Vigneron, Daniel B.

Abstract: Description (Verbatim from the Applicant’s Ab-stract): Prostate cancer is presently the second leading causeof cancer death in American men. Several variables in theoccurrence and natural history of prostate cancer make itespecially difficult to treat. Statistics indicate that less than 1percent of prostate cancers cause clinical disease. Yet whenthey do, the average survival time of patients with metasta-ses is less than two years. Currently there is no reliable wayof predicting which cancers will be indolent versus thosethat will metastasize and result in death. Also as screeningfor these diseases improves, more and earlier stage tumorswill be detected increasing the difficulties in managing thesepatients. A variety of treatment options exist and no consen-sus has been reached on what constitutes the best therapyand how to assess early treatment response, which is onlypoorly addressed by conventional imaging techniques. Anoninvasive method such as Magnetic Resonance Spectro-scopic Imaging (MRSI) to characterize prostate cancersbased on cellular function and metabolism would be an ex-tremely valuable tool for the clinical management of prostatecancer. In this project, we will develop new techniques to

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