CNR Institute of Clinical Physiology Positron Emission Tomography & Radiopharmaceutical Chemistry Dept. PET Tracers Developments Dr. Piero A. Salvadori

CNR Institute of Clinical PhysiologyPositron Emission Tomography & Radiopharmaceutical Chemistry Dept.

PET Tracers Developments

Dr. Piero A. SalvadoriHead, PET & Radiopharm. Chem. Dept.

CNR Inst. Clinical Physiology - Pisa, Italy


FDG is the most common tracer for PET : 85-90% of today PET studies are ‘sugar’ studies


Fluorine-18 Basic facts

Target products Tracers

18F-Fluoride

18F-F2

18F-Tracers

18F-DOPA

18F-Tracers

18F-Tracers

18F-FDG


FDG DESCRIPTION

Isotope Fluorine-18 (18F) Half life (t½) 110 minNuclear Reaction18O(p,n)18F

20Ne(d,)18F

The most important production route

18O(p,n)18F - water targetTarget Material 18O-enriched water

Target Product 18F-fluorideNuclear Reaction Efficiency high (4 on a scale 1-5)Other Methods

20Ne(d,)18F- gas target Target Material Neon gas + F2-gas

Target Product 18F-F2

Nuclear Reaction Efficiency low (1 on a scale 1-5)The inexpensive way to produce “electrophilc” fluorineUsed in deuteron machines


FDG - Applications

- Oncology

- Cardiology

- Neurology

Lung cancer

Colon cancerBreast cancer

Myocardial Viability

Brain Tumours

Parkinson

Alzheimer

Back to Main Applications


FDG - Lung cancer/Colon cancer

FDG whole body scan showing lung cancer

FDG whole body scan showing colon cancer


F-DOPAF-DOPA is accumulated in specific brain structures.

Low activity of F-DOPA in these structures mayindicate Parkinson.

The low activity is demonstrated long before external clinical signs are found in the patient.

F-DOPA


13N-Ammonia FDG

Matching of low FDG up-take and flow restriction

(13N-ammonia)

13N-Ammonia is used for investigation of blood flow in heart, usually together with FDG

Isotope Nitrogen-13 (13N) Half life (t½) 10 min Nuclear Reaction 16O(p,)13NType of target liquid target


ApplicationUsed for measuring of regional cerebral blood flow (rCBF). The water is injected either as a bolus or continuously.

Used for visualising oxygen metabolism, usually in the brain.

Used for measurement of regional cerebral blood volume (rCBV) in combination with 15O-Oxygen gas.

15O-tracersTracer• Water (H2

15O)

• Oxygen gas (15O-O2)

• Carbon Monoxide(C15O)


Carbon-11 basic facts

11C-Methane

11C-Carbon Dioxide

Target products Precursors Tracers

11C-X

11C-Methyl Iodide

11C-Carbon Monoxide

11C-Cyanide

11C-Tracers

11C-Tracers

11C-Tracers

11C-TracersNon GE Products

GE Products

11C-Tracers


11C-Based Tracers

Methionine Oncology; e.g CNS-tumours like pituitary and gliomas; also whole body

Spiperone Dopaminergic system, e.g. Parkinson

Raclopride Dopaminergic system, e.g. Parkinson

Flumazenil Benzodiazepine Receptors; treatment of anxiety, insomnia and epilepsy

Carfentanil Opiate receptor, pain

Tracers from Carbon Dioxide

Acetate used for myocardial viability studies and myocardial blood flow investigations

Tracers from Methyl Iodide


An Example : 11C-Methionine

Whole body methionine scan on a patient with lymphoma


Tracers Application Tracers Application

13N-NH3 Cardiac Blood Flow

18F-FDG glucose metabolism 2-[18F]FDG, FDG glucose metabolism

15O-O2 Oxygen metabolism [18F]Long chain fatty acids

(e. g. [18F] FTHA)beta-oxidation

H215O rCBF [18F] Misonidazole hypoxic cells

[18F]N-Methylbenperidol D2-receptor

Tracers produced with 11 C-CH 3 I

[18F]N-Methylspiperone D2-receptor

[11C] Methionine protein synthesis 16a -[18F] Fluoroestradiol breast tumor studies

[11C] Raclopride D2-receptor [18F] Altanserine S2-receptor

[11C]

Metahydroxyephedrine

adrenergic innevation of the heart Tracers produced with [18F]F2 by Electrophilic Substitution

[11C] Methylspiperone D2-receptor 6-[ 18F]Fluoro-L-dopa, Dopa,

Fluorodopa

presynaptic dopaminergic function

Tracers produced with 11C-CO2

4-[ 18F]Fluoro-L-m-tyrosine,

Tyrosine, Fluorotyrosine

presynaptic dopaminergic function

[11C] Acetate myocordial oxygen consumption 2-[ 18F]Fluoro-L-tyrosine protein synthesis

[11C] Palmitate beta-oxidation 5-[ 18F]Fluorouracil, Uracil,

Fluorouraciltumor therapy control

Tracers produced with 18F- by Nucleophilic Substitution


Other 18F Based Tracers

FMiso - Hypoxic cells (radiotherapy)FLT – prolification cells studies (oncology)

Both tracers are produced with Nucleophilic Substitution Process

For the production of both tracers standard techniques are used. After the final product is synthesized it has to be purified to separate the product from the side compounds produced during

the synthesis.


Other Isotopes – New Developments

A vide range of other isotopes are also possible to produce withPET cyclotrons

Some examples - 124I, 67Br, 64Cu, 94mTc, 86Y

Produced on solid targets - the beam hits a solid material instead of agas or a liquid

These compounds may be very important in the future in conjunctionwith Molecular Imaging/DiagnosticsThese nuclides have longer half life compared to the normal PET-isotopes - several hours to 2-4 days


Future : How Tracers Production is changing……..From ‘conventional’ tracers….

FDG To new cyclotron generated ‘metabolic’ tracers, probes, for monitoring specific processes at molecular/ DNA level.

Metastases from prostate

Cancer (MSKCC)

The incoming new approach :

Target ID : Overactive Androgen-receptor in aggressive prostate cancer metastases

Probe : 18FDHT (Fluoro-dihydrotestosterone)

Imaging : PET


FDG FDHT

AR Prostate Cancer Imaging …MSKCC, Preliminary Results


Point-and-click quantitation software with automatic tumor segmentationIncrease throughput and remove operator dependence

in determination of tumor boundaries

Glenoid and Supra-clavicular

nodes

Upper Thoracic Spine

node

AR Prostate Cancer Imaging …GE CRD, Semi-Auto Segmentation


General Remarks/Conclusions

• Most of public Healthcare Systems as well as reimbursement private bodies require recognized quality standards to providers of medical care (hospitalization, diagnosis, therapy)

• PET scans as well as PET tracers are involved

• There is a general will to foster the international harmonization of rules (e.g. ICH)


Particular remarks• The process of introducing regulations into

PET Centers as well as in PET procedures is expected to continue.

• PET Community is involved into this process and asks Authorities for “ad hoc” regulations which are able to take into account the peculiarity of PET tracers

• PET equipment manufacturers have a substantial role as “providers” of technologies and methods

Documents

CNR Institute of Clinical Physiology Positron Emission Tomography & Radiopharmaceutical Chemistry Dept. PET Tracers Developments Dr. Piero A. Salvadori