WEKO3
アイテム
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Our previous\nstudy showed that [11C]PBB3 was rapidly decomposed to a polar\nradiometabolite in the plasma of mice. For the pharmacokinetic evaluation\nof [11C]PBB3 it is important to elucidate the characteristics of\nradiometabolites. In this study, we identified the chemical structure of a\nmajor radiometabolite of [11C]PBB3 and proposed the metabolic pathway of\n[11C]PBB3.\nMethods: Carrier-added [11C]PBB3 was injected into a mouse for in vivo\nmetabolite analysis. The chemical structure of a major radiometabolite was\nidentified using LC–MS. Mouse and human liver microsomes and liver S9\nsamples were incubated with [11C]PBB3 in vitro. In silico prediction\nsoftware was used to assist in the determination of the metabolite and\nmetabolic pathway of [11C]PBB3.\nResults: In vivo analysis showed that the molecular weight of a major\nradiometabolite of [11C]PBB3, which was called as [11C]M2, was m/z 390\n[M+H+]. In vitro analysis assisted by in silico prediction showed that\n[11C]M2, which was not generated by cytochrome P450 enzymes (CYPs),\nwas generated by sulfated conjugation mediated by a sulfotransferase.\nConclusion: The major radiometabolite, [11C]M2, was identified as a\nsulfated conjugate of [11C]PBB3. 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Identification of a major radiometabolite of [11C]PBB3
https://repo.qst.go.jp/records/47379
https://repo.qst.go.jp/records/4737924d72d06-cb1d-4e2d-9409-1972d3cd4538
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2016-01-18 | |||||
タイトル | ||||||
タイトル | Identification of a major radiometabolite of [11C]PBB3 | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
アクセス権 | ||||||
アクセス権 | metadata only access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
著者 |
Hashimoto, Hiroki
× Hashimoto, Hiroki× Kawamura, Kazunori× Takei, Makoto× Igarashi, Nobuyuki× Fujishiro, Tomoya× Shiomi, Satoshi× Ryuji, Watanabe× Muto, Masatoshi× Furutsuka, Kenji× Ito, Takehito× Yamasaki, Tomoteru× Yui, Joji× Nemoto, Kazuyoshi× Kimura, Yasuyuki× Higuchi, Makoto× Zhang, Ming-Rong× 橋本 裕輝× 河村 和紀× 武井 誠× 五十嵐 延行× 藤代 智也× 潮見 聡× 渡辺 竜二× 武藤 正敏× 古塚 賢士× 伊藤 岳人× 山崎 友照× 由井 譲二× 根本 和義× 木村 泰之× 樋口 真人× 張 明栄 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | 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. |
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書誌情報 |
Nuclear Medicine and Biology 巻 42, 号 12, p. 905-910, 発行日 2015-11 |
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出版者 | ||||||
出版者 | Elsevier | |||||
PubMed番号 | ||||||
識別子タイプ | PMID | |||||
関連識別子 | 26420569 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | doi:10.1016/j.nucmedbio.2015.08.006 |