Radiochemistry and Radiopharmacy III
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1 Radiochemistry and Radiopharmacy III Compact course held at UFSCAR, September Ulrich Abram Freie Universität Berlin Institute of Chemistry and Biochemistry Radiochemistry and Radiopharmacy 1. Fundamentals of Radiochemistry. 2. Radiation and Biology. Basics in Nuclearmedical Diagnostics and Therapy. 3. Positron Emission Tomography (PET) with F Compounds. 4. Single Photon Computer Tomography (SPECT) with 99m Tc. 5. Nuclearmedical Research for Diagnostics ( 99m Tc, 68 Ga) and Therapy ( 6 Re, 8 Re). 1
2 Radiochemistry and Radiopharmacy 3. Positron Emission Tomography (PET) with F Compounds.. - Isotope production with a cyclotron - Positron radiation and PET imaging - Principles of synthetic organic chemistry with F - F-Desoxyglucose (FDG) - Synthesis and use of advanced F radiopharmaceuticals - Multi-method imaging Periodic Table of Elements 2
3 Table of nuclides (Chart of Nuclides) protons neutrons Table of nuclides protons neutrons 3
4 Table of nuclides Table of nuclides 4
5 F as Positron Emitter Nuclear Stability in General F as Positron Emitter Emission Nuclear Stability of a positron in General (ß + -particle) - atomic number decreases by one unit - mass number remains unchanged - typical for nuclides with excess of protons - internal conversion of a proton into a neutron (+ positron + neutrino) ß + Decay: p( nucleus ) n( nucleus + e + ν ) - formation of a neutrino is required from the Laws of the conservation of the spin and energy - similar process like the ß - -decay - emission of a neutrino 1 0 5
6 F as Positron Emitter Emission of a positron (ß + -particle) Annihilation of a positron - a positron is not stable and reacts immediately with an electron under formation of two γ-quants - transformation of matter into energy - no ß + -spectra are measured - instead of this, two γ-quants with distinct energy ( 500 kev) can be detected (E = m c 2 ) - the angle between the quants is exactly 0 Production of F in a cyclotron Nuclear reaction: Target: Proton energy: Irradiation time: O (p,n) F O-enriched water MeV 2 h Cyclotron 6
7 Production of F in a cyclotron Cyclotron Cyclotron centre Production of F in a cyclotron H 2 O target Fluoride separation N ion exchange + K 2 CO 3 + O O O O O O [K(cryptant)] F N Nuclear properties - half- life: min. - γ-energy: MeV cryptant-[2,2,2] 7
8 Production of F-labelled compounds Glucose DOPA Glucose metabolism Methyltyrosin Thymidin Neurotransmitter, receptors Uracil Metabolism of amino acids DNA/RNA synthesis Therapy, pharmacokinetics Production of F-labelled compounds F Fluorodesoxyglucose F DOPA Glucose metabolism Neurotransmitter, receptors F Methyltyrosin F Fluorothymidin F 5-Fluorouracil Metabolism of amino acids DNA/RNA synthesis Therapy, pharmacokinetics 8
9 F-Fluorodesoxyglucose (FDG) Synthesis - Reaction scale: up to GBq F-Fluorodesoxyglucose (FDG) Automated synthesis modul Product F FDG in isotonic saline / citrate buffer 9
10 F-Fluorodesoxyglucose (FDG) Quality control - Gas chromatography: acetonitrile, EtOH - HPLC: residual glucose and side products - radiochemical purity: HPLC, TLC, certified isotope synthesis competing nuclear reactions: O (p,2n) 17 F (t 1/2 = 64.8 sec.) - Sterility and endoxin (pyrogen) testing 16 O (p,α) 13 N (t 1/2 = 9.96 min) 109 Cd (from silver target) 48 V (spallation from Zn) Positron emission tomography (PET) F as Positron Emitter Annihilation of a positron - a positron is not stable and reacts immediately with an electron under formation of two γ-quants - transformation of matter into energy - no ß + -spectra are measured - instead of this, two γ-quants with distinct energy can be detected (E = m c 2 ) - the angle between the quants is exactly 0 10
11 Positron emission tomography (PET) The principle Positron emission tomography (PET) Classical positron emission tomograph 11
12 Positron emission tomography (PET) Slice images brain myocardium tumor Positron emission tomography (PET) Three dimensional reconstitution 12
13 Positron emission tomography (PET) PET/CT combination unit Positron emission tomography (PET) PET/CT combination Muscels and skeleton Diffuse metastases 13
14 Positron emission tomography (PET) PET/MRT combination unit F 15F 16F 17F proton, EC, positron F 19F 20F 21F 22F 23F 24F (ß+) 25F 26F 27F 28F 29F 30F 31F 27F 28F 29F 30F 31F ß- Positron emission tomography (PET) PET/MRT combination Brain Whole body F 15F 16F 17F F proton, EC, positron (ß+) 19F 20F 21F 22F 23F 24F 25F 26F ß-
15 Positron emission tomography (PET) Comparison PET / SPECT - Biological isotopes ( 11 C, 13 N, 15 O, F) - Highly resolved images - visualization of real-time biological activity - Frequently metals ( 99m Tc, 111 In, 131 I) - good resolution - visualization of organ distribution - Too short half-lifes (20 min, 10 min, 2 min, 110 min) - High price (about $ per study) - Suitable half-lifes (6 h, 2.8 d, 8 d) - reasonable price ( $ per study) Positron emission tomography (PET) Radiation dose X-ray teeth images thorax images mammography bile renal tract 0,01 msv 0,03 msv 0,50 msv 4,00 msv 5,00 msv CT head 3 msv CT thorax 10 msv CT gastroindestinal 20 msv Nuclear medicine PET ( F-FDG) 7 msv Nuclear medicine PET ( F-FDG) / CT Bronchial carzinome 15 msv Lymphome 10 msv German Radiation Protection Commission, 2005 Nuclear medicine SPECT ( 99m Tc) kidney function study brain perfusion myocardial diagnostics thyroid liver scintigraphy Skeleton study 1,3 msv 2,0 msv 3,0 msv 1,0 msv 4,0 msv 4,5 msv - Mean natural radiation dose in Germany in 1999: about 2,4 msv/a (1-10 depending on the geographic situation) - Legal annual dose limit für radiation workers: 20 msv Statistics: Bundesamt für Strahlenschutz,
16 PET in research and development Small animal PET PET in research and development PET study in neurosciences Society for Nuclear Medicine,
17 PET in research and development PET scan with F- labelled Dopamin 17
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