@article{oai:repo.qst.go.jp:00047379,
 author = {Hashimoto, Hiroki and Kawamura, Kazunori and Takei, Makoto and Igarashi, Nobuyuki and Fujishiro, Tomoya and Shiomi, Satoshi and Ryuji, Watanabe and Muto, Masatoshi and Furutsuka, Kenji and Ito, Takehito and Yamasaki, Tomoteru and Yui, Joji and Nemoto, Kazuyoshi and Kimura, Yasuyuki and Higuchi, Makoto and Zhang, Ming-Rong and 橋本 裕輝 and 河村 和紀 and 武井 誠 and 五十嵐 延行 and 藤代 智也 and 潮見 聡 and 渡辺 竜二 and 武藤 正敏 and 古塚 賢士 and 伊藤 岳人 and 山崎 友照 and 由井 譲二 and 根本 和義 and 木村 泰之 and 樋口 真人 and 張 明栄},
 issue = {12},
 journal = {Nuclear Medicine and Biology},
 month = {Nov},
 note = {Introduction: [11C]PBB3 is a clinically used positron emission tomography
(PET) probe for in vivo imaging of tau pathology in the brain. Our previous
study showed that [11C]PBB3 was rapidly decomposed to a polar
radiometabolite in the plasma of mice. For the pharmacokinetic evaluation
of [11C]PBB3 it is important to elucidate the characteristics of
radiometabolites. In this study, we identified the chemical structure of a
major radiometabolite of [11C]PBB3 and proposed the metabolic pathway of
[11C]PBB3.
Methods: Carrier-added [11C]PBB3 was injected into a mouse for in vivo
metabolite analysis. The chemical structure of a major radiometabolite was
identified using LC–MS. Mouse and human liver microsomes and liver S9
samples were incubated with [11C]PBB3 in vitro. In silico prediction
software was used to assist in the determination of the metabolite and
metabolic pathway of [11C]PBB3.
Results: In vivo analysis showed that the molecular weight of a major
radiometabolite of [11C]PBB3, which was called as [11C]M2, was m/z 390
[M+H+]. In vitro analysis assisted by in silico prediction showed that
[11C]M2, which was not generated by cytochrome P450 enzymes (CYPs),
was generated by sulfated conjugation mediated by a sulfotransferase.
Conclusion: The major radiometabolite, [11C]M2, was identified as a
sulfated conjugate of [11C]PBB3. [11C]PBB3 was metabolized mainly by a sulfotransferase and subsidiarily by CYPs.},
 pages = {905--910},
 title = {Identification of a major radiometabolite of [11C]PBB3},
 volume = {42},
 year = {2015}
}