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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
CNR Institute of Clinical PhysiologyPositron Emission Tomography & Radiopharmaceutical Chemistry Dept.
FDG is the most common tracer for PET : 85-90% of today PET studies are ‘sugar’ studies
CNR Institute of Clinical PhysiologyPositron Emission Tomography & Radiopharmaceutical Chemistry Dept.
Fluorine-18 Basic facts
Target products Tracers
18F-Fluoride
18F-F2
18F-Tracers
18F-DOPA
18F-Tracers
18F-Tracers
18F-FDG
CNR Institute of Clinical PhysiologyPositron Emission Tomography & Radiopharmaceutical Chemistry Dept.
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
CNR Institute of Clinical PhysiologyPositron Emission Tomography & Radiopharmaceutical Chemistry Dept.
FDG - Applications
- Oncology
- Cardiology
- Neurology
Lung cancer
Colon cancerBreast cancer
Myocardial Viability
Brain Tumours
Parkinson
Alzheimer
Back to Main Applications
CNR Institute of Clinical PhysiologyPositron Emission Tomography & Radiopharmaceutical Chemistry Dept.
FDG - Lung cancer/Colon cancer
FDG whole body scan showing lung cancer
FDG whole body scan showing colon cancer
CNR Institute of Clinical PhysiologyPositron Emission Tomography & Radiopharmaceutical Chemistry Dept.
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
CNR Institute of Clinical PhysiologyPositron Emission Tomography & Radiopharmaceutical Chemistry Dept.
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
CNR Institute of Clinical PhysiologyPositron Emission Tomography & Radiopharmaceutical Chemistry Dept.
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)
CNR Institute of Clinical PhysiologyPositron Emission Tomography & Radiopharmaceutical Chemistry Dept.
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
CNR Institute of Clinical PhysiologyPositron Emission Tomography & Radiopharmaceutical Chemistry Dept.
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
CNR Institute of Clinical PhysiologyPositron Emission Tomography & Radiopharmaceutical Chemistry Dept.
An Example : 11C-Methionine
Whole body methionine scan on a patient with lymphoma
CNR Institute of Clinical PhysiologyPositron Emission Tomography & Radiopharmaceutical Chemistry Dept.
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
CNR Institute of Clinical PhysiologyPositron Emission Tomography & Radiopharmaceutical Chemistry Dept.
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.
CNR Institute of Clinical PhysiologyPositron Emission Tomography & Radiopharmaceutical Chemistry Dept.
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
CNR Institute of Clinical PhysiologyPositron Emission Tomography & Radiopharmaceutical Chemistry Dept.
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
CNR Institute of Clinical PhysiologyPositron Emission Tomography & Radiopharmaceutical Chemistry Dept.
FDG FDHT
AR Prostate Cancer Imaging …MSKCC, Preliminary Results
CNR Institute of Clinical PhysiologyPositron Emission Tomography & Radiopharmaceutical Chemistry Dept.
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
CNR Institute of Clinical PhysiologyPositron Emission Tomography & Radiopharmaceutical Chemistry Dept.
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)
CNR Institute of Clinical PhysiologyPositron Emission Tomography & Radiopharmaceutical Chemistry Dept.
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
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