64 cu radioisotope production capability at ANSTOs national medical cyclotron AUSTRALIAN NUCLEAR SCIENCE AND TECHNOLOGY ORGANISATION radiopharmaceutical research institute medical radioisotope development project r

AUSTRALIAN NUCLEAR SCIENCE AND TECHNOLOGY ORGANISATION Radiopharmaceutical Research Institute Medical Radioisotope Development Project RRI-0168 64 Cu radioisotope production capability at ANSTO’s National Medical Cyclotron Le Van So ANSTO, 01 January 2008 A Introduction 64 Cu is a radionuclide of high interest for nuclear medicine use with the following major advantages Advantageous properties Beta and positron emitter ( 39% β- and 17.4 % β+ ) of half-life of 12.7 hours can play a role of bi-functional radioisotope for both PET imaging and endoradiotherapy (ERT) Radiotherapeutic advantages: • • β- energy, β max =0.578 MeV (39 %).Low tissue penetration is suitable for treatment of small tumors Electron capture decay with its associated Auger emission can yield more efficient cell killing Diagnostic imaging advantages: • β+ emission (17.4 % ) for PET imaging Advantageous chelating chemistry useful for labelling biomolecules via strong formation of stable coordinative complexes with bifunctional chelators 1-2 - acyclic polyaminocarboxylate (DTPA, EDTA), cyclic polyamines (Cyclam) and macrocyclic polyaminocarboxylates (TETA, DOTA, NOTA) Bio-molecule labelling: • • The 64,67Cu-Chelator-antibody conjugates (MAb35-against carcinoembryonic antigen, SEN7 and SWA20-against lung cancer antigen, VG76e, B72.3 antibodies) The 64Cu labelled ligands targeting receptors (64Cu-DOTA-[Pro1, Tyr4]bombesin[1-14] for targeting GRP receptors , 64Cu-TETA-somatostatin analogs, 64 Cu-DOTA-Annexin V, ) are conjugates being widely investigated 64 Cu’s preferable properties involved in physiological pathways 1-4 make radioactive Copper complex molecules useful (in their own right) as targeting radiopharmaceuticals, PTSM for brain and myocardial imaging studies and PTSM & ATSM for tumour treatment Production capability Two cyclotron based methods are used for 64Cu production 64 Cu preparation based on the 64Ni target • • Advantages: - No side-nuclear reactions which could induce radionuclidic impurities in the 64Cu product - High 64Cu yield Disadvantages: - Very expensive enriched 64Ni target - The larger cyclotron with proton beam energy not adjustable to lower than 13 MeV is difficult to be used for the 64Ni target based 64Cu production due to the need for a larger amount of 64Ni target and a special target design 64 Cu preparation based on the 68Zn target • • Advantage: - This production route seems more economic in the target utilisation, because both 67Ga and 64Cu can be produced from the same low cost target Disadvantages - Radiochemical separation is more complex - High potential of contamination from several impure radionuclides - Low 64Cu yield B Production procedures I 64 Cu preparation based on the 64Ni target Target & irradiation Target: Isotopically enriched 64Ni metal target material are purchased from TraceSciences International Inc.USA Target isotopic compositions : 64Ni (98.0 %), 58Ni (