WEKO3
アイテム
IN VIVO, IN VITRO, AND IN SILICO EVALUATION OF RADIOMETABOLITE OF [11C]PBB3 AS A CLINICALLY USEFUL PET PROBE FOR IMAGING OF TAU PATHOLOGY.
https://repo.qst.go.jp/records/71873
https://repo.qst.go.jp/records/718731a5b3350-d2b4-491b-a092-a364fc73fd37
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2015-11-25 | |||||
| タイトル | ||||||
| タイトル | IN VIVO, IN VITRO, AND IN SILICO EVALUATION OF RADIOMETABOLITE OF [11C]PBB3 AS A CLINICALLY USEFUL PET PROBE FOR IMAGING OF TAU PATHOLOGY. | |||||
| 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_c94f | |||||
| 資源タイプ | conference object | |||||
| 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 |
|||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Objectives: 2-((1E,3E)-4-(6-(11C-methylamino)pyridin-3-yl)buta-1,3-dienyl) benzo[d]thiazol-6-ol ([11C]PBB3, Fig. 1) is a clinically useful PET probe for in vivo imaging of tau pathology in the brain. For the pharmacokinetic evaluation of [11C]PBB3, it is important to elucidate the characteristics of radiometabolites. In this study, we evaluated radiometabolite after injection of [11C]PBB3 in mice brain and plasma, identified the chemical structure of a major radiometabolite of [11C]PBB3, and proposed the metabolic pathway of [11C]PBB3. Methods: [11C]PBB3 was synthesized by reaction of the tert-butyldimethylsilyl desmethyl precursor with [11C]methyl iodide using potassium hydroxide as a base, followed by deprotection. [11C]PBB3 or carrier-added [11C]PBB3 was injected into a mouse for in vivo metabolite analysis. The chemical structure of a major radiometabolite was identified using radio-HPLC and LC–MS. Mouse and human liver microsomes and liver S9 samples were incubated with [11C]PBB3 in vitro, and its radiometabolite was analyzed using radio-HPLC. In silico prediction software was used to assist in the determination of the metabolite and metabolic pathway of [11C]PBB3. Results and discussion: In in vivo metabolite study, more than 70% of total radioactivity in the mouse brain homogenate at 5 min after injection represented the parent [11C]PBB3, despite its rapid metabolism in the plasma. Also, in vivo metabolite study using carrier-added [11C]PBB3 showed that the molecular weight of a major radiometabolite of [11C]PBB3, which was called as [11C]M2 (Fig. 1), was m/z 390 [M+H+]. In vitro metabolite study 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. Our data demonstrated that [11C]PBB3 was mainly metabolized to [11C]M2 by sulfate conjugation mediated by sulfotransferases, and a minor radiometabolite, [11C]M1 (Fig. 1), was yielded through oxidation mediated by CYPs. These results suggest that [11C]M2 may be retained in the plasma, recirculated throughout the whole body, and may gradually enter the brain notwithstanding its relatively high polarity. Conclusion: [11C]PBB3 was rapidly decomposed to a polar radiolabeled metabolite in the plasma. The major radiometabolite, [11C]M2, was identified as a sulfated conjugate of [11C]PBB3. [11C]PBB3 was metabolized mainly by a sulfotransferase and subsidiary by CYPs. |
|||||
| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Ninth Japan-China Joint Seminar on Radiopharmaceutical Chemistry | |||||
| 発表年月日 | ||||||
| 日付 | 2015-11-09 | |||||
| 日付タイプ | Issued | |||||
