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Positron Emission Tomography (PET) is an advanced non-invasive technology used in the field of nuclear medicine for clinical diagnosis using radiotracers labeled with short-lived positron emitting radionuclides such as (11)C (half-life: 20.4 min), (13)N, (15)O and (18)F. The present study describes an efficient rapid synthesis method for [(11)C]Phosgene ([(11)C]COCl(2)) which is an important potential precursor for preparation of PET radiopharmaceuticals. Catalytic oxidation of [(11)C]CCl(4) using Fe(2)O(3) powder mixed with Fe granules as an oxidizing agent was newly accomplished with a development of fully automated synthetic apparatus. Utilization of produced [(11)C]COCl(2) provided a substantial synthesis of [2-(11)C]thymine as a key intermediate for preparation of [2-(11)C]thymidine, a PET tracer to evaluate cellular proliferation. Direct ring closure reaction of the alkali metal salt of beta-(N-benzoyl-amino)methacrylamide with [(11)C]COCl(2) readily proceeded under mild conditions to afford [2-(11)C]thymine in fair yield reproducibly. By way of further application, a useful PET ligand for beta-adrenoreceptors, S-(-)-[(11)C]CGP-12177 (CGP) was synthesized in markedly high yield with high specific activity and radiochemical purity. CGP for intravenous injection was prepared in 25 min after EOB with a yield of 1.5+/-0.2 GBq. These results of quality control tests demonstrated that CGP preparation is suitable for routine clinical use. Thus, CGP-PET study has been newly added to clinical PET for cardiac functional investigation in Hokkaido University Hospital.

A Study on the Highly Efficient Synthesis and Pharmaceutical Evaluation of PET Radiopharmaceuticals for the Clinical Application