title: Synthesis of [¹¹C]uric acid, using [¹¹C]phosgene, as a possible biomarker in PET imaging for diagnosis of gout.
abstract: The synthesis and in vivo evaluation of (11)C -labeled uric acid ([(11)C]1), a potential imaging agent for the diagnosis of urate-related life-style diseases, was performed using positron emission tomography (PET) image analysis. First, the synthesis of [(11)C]1 was achieved by reacting 5,6-diaminouracil (2) with (11)C-labeled phosgene ([(11)C]COCl(2)). The radiochemical yield of [(11)C]1 was 37±7% (decay-corrected based on [(11)C]COCl(2)) with specific radioactivities of 96-152GBq/μmol at the end of synthesis (n=6). The average time of radiosynthesis from the end of bombardment, including formulation, was about 30min with >98% radiochemical purity. Second, the synthetic approach to [(11)C]1 was optimized using 5,6-diaminouracil sulfate (3) with [(11)C]COCl(2) in the presence of 1,8-bis(dimethylamino)naphthalene. [(11)C]1 was synthesized in 36±6% radiochemical yield, 89-142GBq/μmol of specific radioactivities, and 98% radiochemical purity by this method (n=5). This allowed the synthesis of [(11)C]1 to be carried out repeatedly and the radiochemical yield, specific radioactivities, average time of synthesis, and radiochemical purity of [(11)C]1 were similar to those obtained using 2. PET studies in rats showed large differences in the accumulation of radioligand in the limbs under normal and hyperuricemic conditions. Thus, an efficient and convenient automated synthesis of [(11)C]1 has been developed, and preliminary PET evaluation of [(11)C]1 confirmed the increased accumulation of radioactivity in the limbs of a rat model of hyperuricemia.
authors.affiliation: Molecular Probe Dynamics Laboratory, RIKEN Center for Molecular Imaging Science (CMIS), 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan. k.yashio@riken.jp
authors.forename: Keiji
authors.initials: K
authors.lastname: Yashio
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Katayama
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Takashima
authors.forename: Naoki
authors.initials: N
authors.lastname: Ishiguro
authors.forename: Hisashi
authors.initials: H
authors.lastname: Doi
authors.forename: Masaaki
authors.initials: M
authors.lastname: Suzuki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Wada
authors.forename: Ikumi
authors.initials: I
authors.lastname: Tamai
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D001331:Automation; D015415:Biomarkers / Q000378:metabolism*; D002247:Carbon Isotopes / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004195:Disease Models, Animal; D006073:Gout / Q000175:diagnosis* / Q000473:pathology*; D033461:Hyperuricemia / Q000175:diagnosis; D007091:Image Processing, Computer-Assisted; D008956:Models, Chemical; D010705:Phosgene; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D013696:Temperature; D014527:Uric Acid
chemical_list: D015415:Biomarkers; D002247:Carbon Isotopes; D010705:Phosgene; D014527:Uric Acid