title: [Study on the highly efficient synthesis and pharmaceutical evaluation of PET radiopharmaceuticals for the clinical application].
abstract: 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.
authors.affiliation: Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Japan. nishijim@hoku-iryo-u.ac.jp
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Nishijima
mesh_terms: D000818:Animals; D002625:Chemistry, Organic / Q000379:methods*; D004341:Drug Evaluation; D006801:Humans; D007553:Isotope Labeling / Q000379:methods*; D010705:Phosgene / Q000138:chemical synthesis*; D049268:Positron-Emission Tomography; D011412:Propanolamines / Q000138:chemical synthesis*; D011829:Radiation Dosage; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D013936:Thymidine / Q000138:chemical synthesis
chemical_list: D011412:Propanolamines; D019275:Radiopharmaceuticals; D010705:Phosgene; C033394:CGP 12177; D013936:Thymidine