{"created":"2023-05-15T14:38:21.560667+00:00","id":49507,"links":{},"metadata":{"_buckets":{"deposit":"aca69a13-d715-4652-8536-5510c7e73478"},"_deposit":{"created_by":1,"id":"49507","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"49507"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00049507","sets":["1"]},"author_link":["798399","798423","798411","798405","798415","798403","798400","798418","798412","798420","798402","798416","798414","798422","798408","798406","798410","798421","798401","798407","798413","798419","798404","798409","798424","798417"],"item_8_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2018-12","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"2","bibliographicPageEnd":"698","bibliographicPageStart":"688","bibliographicVolumeNumber":"62","bibliographic_titles":[{"bibliographic_title":"Jounal of Medicinal Chemistry"}]}]},"item_8_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Phosphodiesterase 10A (PDE10A) is a newly identified therapeutic target for central nervous system disorders. 2-(2-(3-(4-([18F]Fluoroethoxy)phenyl)-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione ([18F]MNI-659, [18F]5) is a useful positron emission tomography (PET) ligand for imaging of PDE10A in the human brain. However, the radiolabeled metabolite of [18F]5 can accumulate in the brain. In this study, using [18F]5 as a lead compound, we designed four new 18F-labeled ligands ([18F]6–9) to find one more suitable than [18F]5. Of these, 2-(2-(3-(4-([18F]fluoromethoxy-d2)phenyl)-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione ([18F]9) exhibited high in vitro binding affinity (Ki = 2.9 nM) to PDE10A and suitable lipophilicity (LogD = 2.2). In PET studies, the binding potential (BPND) of [18F]9 (5.8) to PDE10A in rat brains was significantly higher than that of [18F]5 (4.6). Furthermore, metabolite analysis showed much lower levels of contamination with radiolabeled metabolites of [18F]9 in the brain than those of [18F]5. In conclusion, [18F]9 is a useful PET ligand for PDE10A imaging in brain.","subitem_description_type":"Abstract"}]},"item_8_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"ACS Publications"}]},"item_8_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1021/acs.jmedchem.8b01366","subitem_relation_type_select":"DOI"}}]},"item_8_relation_17":{"attribute_name":"関連サイト","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://pubs.acs.org/doi/10.1021/acs.jmedchem.8b01366","subitem_relation_type_select":"URI"}}]},"item_8_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0022-2623","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":"Mori, Wakana"}],"nameIdentifiers":[{"nameIdentifier":"798399","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Yamasaki, Tomoteru"}],"nameIdentifiers":[{"nameIdentifier":"798400","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Fujinaga, Masayuki"}],"nameIdentifiers":[{"nameIdentifier":"798401","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ogawa, Masanao"}],"nameIdentifiers":[{"nameIdentifier":"798402","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Yiding"}],"nameIdentifiers":[{"nameIdentifier":"798403","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hatori, Akiko"}],"nameIdentifiers":[{"nameIdentifier":"798404","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Xie, Lin"}],"nameIdentifiers":[{"nameIdentifier":"798405","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kumata, Katsushi"}],"nameIdentifiers":[{"nameIdentifier":"798406","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Wakizaka, Hidekatsu"}],"nameIdentifiers":[{"nameIdentifier":"798407","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kurihara, Yusuke"}],"nameIdentifiers":[{"nameIdentifier":"798408","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ohkubo, Takayuki"}],"nameIdentifiers":[{"nameIdentifier":"798409","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Nengaki, Nobuki"}],"nameIdentifiers":[{"nameIdentifier":"798410","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ming-Rong, Zhang"}],"nameIdentifiers":[{"nameIdentifier":"798411","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Mori, Wakana","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"798412","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Yamasaki, Tomoteru","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"798413","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Fujinaga, Masayuki","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"798414","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ogawa, Masanao","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"798415","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Yiding","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"798416","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hatori, Akiko","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"798417","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Xie, Lin","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"798418","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kumata, Katsushi","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"798419","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Wakizaka, Hidekatsu","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"798420","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kurihara, Yusuke","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"798421","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ohkubo, Takayuki","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"798422","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Nengaki, Nobuki","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"798423","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ming-Rong, Zhang","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"798424","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":"Development of 2-(2-(3-(4-([18F]Fluoromethoxy- d2)phenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione for Positron-Emission-Tomography Imaging of Phosphodiesterase 10A in the Brain.","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Development of 2-(2-(3-(4-([18F]Fluoromethoxy- d2)phenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione for Positron-Emission-Tomography Imaging of Phosphodiesterase 10A in the Brain."}]},"item_type_id":"8","owner":"1","path":["1"],"pubdate":{"attribute_name":"公開日","attribute_value":"2018-12-10"},"publish_date":"2018-12-10","publish_status":"0","recid":"49507","relation_version_is_last":true,"title":["Development of 2-(2-(3-(4-([18F]Fluoromethoxy- d2)phenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione for Positron-Emission-Tomography Imaging of Phosphodiesterase 10A in the Brain."],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T23:51:23.124140+00:00"}