{"created":"2023-05-15T14:35:44.976136+00:00","id":45986,"links":{},"metadata":{"_buckets":{"deposit":"b6781dfd-0fe9-434a-b81f-c2802679975a"},"_deposit":{"created_by":1,"id":"45986","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"45986"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00045986","sets":["1"]},"author_link":["457614","457607","457615","457610","457619","457620","457618","457603","457611","457612","457602","457608","457599","457616","457600","457617","457601","457613","457606","457604","457598","457609","457605","457621"],"item_8_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2010-12","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"2","bibliographicPageEnd":"870","bibliographicPageStart":"861","bibliographicVolumeNumber":"19","bibliographic_titles":[{"bibliographic_title":"Bioorganic & Medicinal Chemistry"}]}]},"item_8_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"The purpose of this study was to synthesize two new positron emission tomography (PET) probes,N-(4-(2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl)phenyl)-9,10-dihydro-5-[18F]fluoroethoxy-9-oxo-4-acridine carboxamide ([18F]3) and quinoline-3-carboxylic acid [2-(4-{2-[7-(2-[18F]fluoroethoxy)-\n6-methoxy-3,4-dihydro-1H-isoquinolin-2-yl]ethyl}phenylcarbamoyl)-4,5-imethoxyphenyl]amide ([18F]4),andtoevaluate thepotentialof thesePETprobes for assessing thefunctionoftwomajor drugefflux transporters,P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). [18F]3 and [18F]4 were synthesized by\n18F-alkylation of each O-desmethyl precursor with [18F]2-fluoroethyl bromide for injection as PET probes. In vitroaccumulation assayshowed that treatmentwith P-gp/BCRPinhibitors (1 and2) enhanced the intracellular accumulation capacity of P-gp- and BCRP-overexpressing MES-SA/Dx5 cells. In PET studies, the uptake (AUCbrain [0–60 min]) of [18F]3 and [18F]4 in wild-type mice co-injected with 1 were approximately sevenfold higher than that in wild-typemice, and the uptake of [18F]3 and [18F]4 in P-gp/Bcrp knockout mice were eightto ninefold higher than that in wild-typemice. The increased uptake of [18F]3 and [18F]4 was similar to that of\nparent compounds([11C]1 and [11C]2) previously described, indicating that radioactivity levels in the brain after injection of [18F]3 and [18F]4 are related to the function of drug efflux transporters. Also, these results suggest that the structural difference between parent compounds ([11C]1 and [11C]2) and fluoroethyl analogs ([18F]3 and [18F]4) do not obviously affect the potency against drug efflux transporters. Inmetabolite analysis of mice, the unchanged form in the brain and plasma at 60min after co-injection of [18F]4 plus 1 were higher (95% for brain; 81% for plasma) than that after co-injection of [18F]3 plus 1. [18F]4 is a promising PET probe to assess the function of drug efflux transporters.","subitem_description_type":"Abstract"}]},"item_8_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1016/j.bmc.2010.12.004","subitem_relation_type_select":"DOI"}}]},"item_8_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0968-0896","subitem_source_identifier_type":"ISSN"}]},"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":"Kawamura, Kazunori"}],"nameIdentifiers":[{"nameIdentifier":"457598","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Yamasaki, Tomoteru"}],"nameIdentifiers":[{"nameIdentifier":"457599","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Konno, Fujiko"}],"nameIdentifiers":[{"nameIdentifier":"457600","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Yui, Joji"}],"nameIdentifiers":[{"nameIdentifier":"457601","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hatori, Akiko"}],"nameIdentifiers":[{"nameIdentifier":"457602","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Yanamoto, Kazuhiko"}],"nameIdentifiers":[{"nameIdentifier":"457603","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Wakizaka, Hidekatsu"}],"nameIdentifiers":[{"nameIdentifier":"457604","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ogawa, Masanao"}],"nameIdentifiers":[{"nameIdentifier":"457605","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Yoshida, Yuichiro"}],"nameIdentifiers":[{"nameIdentifier":"457606","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Nengaki, Nobuki"}],"nameIdentifiers":[{"nameIdentifier":"457607","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Fukumura, Toshimitsu"}],"nameIdentifiers":[{"nameIdentifier":"457608","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Ming-Rong"}],"nameIdentifiers":[{"nameIdentifier":"457609","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"河村 和紀","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"457610","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"山崎 友照","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"457611","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"昆野 富士子","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"457612","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"由井 譲二","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"457613","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"羽鳥 晶子","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"457614","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"柳本 和彦","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"457615","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"脇坂 秀克","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"457616","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"小川 政直","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"457617","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"吉田 勇一郎","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"457618","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"念垣 信樹","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"457619","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"福村 利光","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"457620","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"張 明栄","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"457621","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":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"Synthesis and in vivo evaluation of 18F-fluoroethyl GF120918 and XR9576 as positron emission tomography probes for assessing the function of drug efflux transporters","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Synthesis and in vivo evaluation of 18F-fluoroethyl GF120918 and XR9576 as positron emission tomography probes for assessing the function of drug efflux transporters"}]},"item_type_id":"8","owner":"1","path":["1"],"pubdate":{"attribute_name":"公開日","attribute_value":"2011-01-21"},"publish_date":"2011-01-21","publish_status":"0","recid":"45986","relation_version_is_last":true,"title":["Synthesis and in vivo evaluation of 18F-fluoroethyl GF120918 and XR9576 as positron emission tomography probes for assessing the function of drug efflux transporters"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T23:57:14.380671+00:00"}