PET Tracers Developments Dr. Piero A. Salvadori Head, 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 18F-FDG 18F-Fluoride Target products Tracers 18F-Tracers 18F-Tracers 18F-F2 18F-DOPA 18F-Tracers

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

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

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

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

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

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)

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

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

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

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.

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

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)

AR Prostate Cancer Imaging … MSKCC, Preliminary Results FDG FDHT

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

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