1. PET Tracers Developments
Dr. Piero A. Salvadori
Head, PET & Radiopharm. Chem. Dept.
CNR Inst. Clinical Physiology - Pisa, Italy

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

3. Fluorine-18 Basic facts 18F-FDG 18F-Fluoride Target products Tracers
18F-Tracers
18F-Tracers
18F-F2
18F-DOPA
18F-Tracers

4. The most important production route
FDG DESCRIPTION
Isotope Fluorine-18 (18F) Half life (t½) 110 min Nuclear Reaction 18O(p,n)18F 20Ne(d,)18F
The most important production route
18O(p,n)18F - water target Target Material 18O-enriched water
Target Product 18F-fluoride Nuclear 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” fluorine Used in deuteron machines

5. Back to Main Applications
FDG - Applications
- Oncology
Lung cancer
Colon cancer
Breast cancer
Brain Tumours
- Neurology
Parkinson
Alzheimer
- Cardiology
Myocardial Viability
Back to Main Applications

6. FDG - Lung cancer/Colon cancer
FDG whole body scan showing lung cancer
FDG whole body scan showing colon cancer

7. F-DOPA F-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
F-DOPA

8. Isotope. Nitrogen-13 (13N) Half life (t½). 10 min Nuclear Reaction
Isotope Nitrogen-13 (13N) Half life (t½) 10 min Nuclear Reaction 16O(p,)13N Type of target liquid target
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
13N-Ammonia
FDG

9. 15O-tracers Application Tracer
Used 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-tracers
Tracer
Water (H215O)
Oxygen gas (15O-O2)
Carbon Monoxide (C15O)

10. 11C-Methyl Iodide 11C-Tracers
Carbon-11 basic facts
Target products Precursors Tracers
11C-Tracers
11C-Methyl Iodide
11C-Carbon Dioxide
11C-Tracers
11C-X
11C-Methane
11C-Carbon Monoxide
11C-Tracers
11C-Cyanide
11C-Tracers
GE Products
11C-Tracers
Non GE Products

11. Tracers from Methyl Iodide
11C-Based Tracers
Tracers from Carbon Dioxide
Acetate used for myocardial viability studies and myocardial blood flow investigations
Tracers from Methyl Iodide
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

12. An Example : 11C-Methionine
Whole body methionine scan on a patient with lymphoma

14. FMiso - Hypoxic cells (radiotherapy)
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.

15. Other Isotopes – New Developments
A vide range of other isotopes are also possible to produce with PET cyclotrons Some examples - 124I, 67Br, 64Cu, 94mTc, 86Y Produced on solid targets - the beam hits a solid material instead of a gas or a liquid These compounds may be very important in the future in conjunction with Molecular Imaging/Diagnostics These nuclides have longer half life compared to the normal PET- isotopes - several hours to 2-4 days

16. 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.
The incoming new approach :
Target ID : Overactive
Androgen-receptor in aggressive prostate cancer metastases
Probe : 18FDHT
(Fluoro-dihydrotestosterone)
Imaging : PET
Metastases
from prostate
Cancer (MSKCC)

17. AR Prostate Cancer Imaging …
MSKCC, Preliminary Results
FDG
FDHT

18. AR Prostate Cancer Imaging … GE CRD, Semi-Auto Segmentation
Glenoid and
Supra-clavicular nodes
Upper Thoracic Spine
node
Need to tie in other sophisticated image analysis, quantitation, data mining, computer-aided diagnosis.
Point-and-click quantitation software with automatic tumor segmentation
Increase throughput and remove operator dependence
in determination of tumor boundaries

19. 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)

20. 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