{"created":"2023-05-15T14:52:38.564000+00:00","id":71873,"links":{},"metadata":{"_buckets":{"deposit":"c03bd4dc-6155-4d11-b2b5-12874c152279"},"_deposit":{"created_by":1,"id":"71873","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"71873"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00071873","sets":["10:28"]},"author_link":["707812","707795","707817","707798","707808","707801","707793","707791","707787","707813","707804","707802","707794","707800","707807","707797","707809","707789","707814","707803","707815","707792","707811","707818","707805","707816","707790","707788","707796","707810","707799","707806"],"item_10005_date_7":{"attribute_name":"発表年月日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2015-11-09","subitem_date_issued_type":"Issued"}]},"item_10005_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Objectives: 2-((1E,3E)-4-(6-(11C-methylamino)pyridin-3-yl)buta-1,3-dienyl)\nbenzo[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. \nMethods: [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. \nResults 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.\nConclusion: [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.","subitem_description_type":"Abstract"}]},"item_10005_description_6":{"attribute_name":"会議概要（会議名, 開催地, 会期, 主催者等）","attribute_value_mlt":[{"subitem_description":"Ninth Japan-China Joint Seminar on Radiopharmaceutical Chemistry","subitem_description_type":"Other"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"metadata only access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_14cb"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Hashimoto, Hiroki"}],"nameIdentifiers":[{"nameIdentifier":"707787","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kawamura, Kazunori"}],"nameIdentifiers":[{"nameIdentifier":"707788","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Takei, Makoto"}],"nameIdentifiers":[{"nameIdentifier":"707789","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Igarashi, Nobuyuki"}],"nameIdentifiers":[{"nameIdentifier":"707790","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Fujishiro, Tomoya"}],"nameIdentifiers":[{"nameIdentifier":"707791","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Shiomi, Satoshi"}],"nameIdentifiers":[{"nameIdentifier":"707792","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ryuji, Watanabe"}],"nameIdentifiers":[{"nameIdentifier":"707793","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Muto, Masatoshi"}],"nameIdentifiers":[{"nameIdentifier":"707794","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Furutsuka, Kenji"}],"nameIdentifiers":[{"nameIdentifier":"707795","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ito, Takehito"}],"nameIdentifiers":[{"nameIdentifier":"707796","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Yamasaki, Tomoteru"}],"nameIdentifiers":[{"nameIdentifier":"707797","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Yui, Joji"}],"nameIdentifiers":[{"nameIdentifier":"707798","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Nemoto, Kazuyoshi"}],"nameIdentifiers":[{"nameIdentifier":"707799","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kimura, Yasuyuki"}],"nameIdentifiers":[{"nameIdentifier":"707800","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Higuchi, Makoto"}],"nameIdentifiers":[{"nameIdentifier":"707801","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Ming-Rong"}],"nameIdentifiers":[{"nameIdentifier":"707802","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"橋本 裕輝","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"707803","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"河村 和紀","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"707804","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"武井 誠","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"707805","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"五十嵐 延行","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"707806","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"藤代 智也","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"707807","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"潮見 聡","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"707808","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"渡辺 竜二","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"707809","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"武藤 正敏","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"707810","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"古塚 賢士","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"707811","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"伊藤 岳人","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"707812","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"山崎 友照","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"707813","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"由井 譲二","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"707814","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"根本 和義","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"707815","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"木村 泰之","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"707816","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"樋口 真人","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"707817","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"張 明栄","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"707818","nameIdentifierScheme":"WEKO"}]}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"conference object","resourceuri":"http://purl.org/coar/resource_type/c_c94f"}]},"item_title":"IN VIVO, IN VITRO, AND IN SILICO EVALUATION OF RADIOMETABOLITE OF [11C]PBB3 AS A CLINICALLY USEFUL PET PROBE FOR IMAGING OF TAU PATHOLOGY.         ","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"IN VIVO, IN VITRO, AND IN SILICO EVALUATION OF RADIOMETABOLITE OF [11C]PBB3 AS A CLINICALLY USEFUL PET PROBE FOR IMAGING OF TAU PATHOLOGY.         "}]},"item_type_id":"10005","owner":"1","path":["28"],"pubdate":{"attribute_name":"公開日","attribute_value":"2015-11-25"},"publish_date":"2015-11-25","publish_status":"0","recid":"71873","relation_version_is_last":true,"title":["IN VIVO, IN VITRO, AND IN SILICO EVALUATION OF RADIOMETABOLITE OF [11C]PBB3 AS A CLINICALLY USEFUL PET PROBE FOR IMAGING OF TAU PATHOLOGY.         "],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T19:46:24.587019+00:00"}