{"created":"2023-05-15T14:58:51.314615+00:00","id":79840,"links":{},"metadata":{"_buckets":{"deposit":"b9a5a1b7-ddd1-4a9d-8fd0-fe961400cb7a"},"_deposit":{"created_by":1,"id":"79840","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"79840"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00079840","sets":["1"]},"author_link":["1027173","1027168","1027174","1027176","1027166","1027177","1027169","1027175","1027161","1027167","1027160","1027170","1027162","1027171","1027172","1027164","1027165","1027163"],"item_8_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2020-04","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"3","bibliographicPageEnd":"360","bibliographicPageStart":"353","bibliographicVolumeNumber":"373","bibliographic_titles":[{"bibliographic_title":"The Journal of Pharmacology and Experimental Therapeutics"}]}]},"item_8_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Fatty acid amide hydrolase (FAAH) is a key enzyme in the endocannabinoid system. N-(3,4-Dimethylisoxazol-5-yl)piperazine-4-[4-(2-fluoro-4-[11C]methylphenyl)thiazol-2-yl]-1-carboxamide ([11C]DFMC) was developed as an irreversible-type positron emission tomography (PET) ligand for FAAH. Here, we attempted to noninvasively estimate rate constant k3 as a direct index for FAAH in the rat brain. First, the two-tissue compartment model analysis including three parameters (K1–k3, 2TCMi) in PET study with [11C]DFMC was conducted, which provided 0.21 ± 0.04 mL·cm−3·min−1 of the net uptake value (Ki), an indirect index for FAAH, in the FAAH-richest region (the cingulate cortex). Subsequently, to noninvasively estimate Ki value, the reference model analysis (Patlak Reference, PGAREF) was tried using a time-activity curve of the spinal cord. In that result, the noninvasive Ki value (KREF) was concisely estimated with high correlation (r > 0.95) to Ki values based on 2TCMi. Using estimated KREF value, we tried to obtain calculated-k3 based on previously defined equations. The caluculated-k3 was successfully estimated with high correlation (r = 0.95) to direct k3 in 2TCMi. Finally, the dose relationship study using calculated-k3 demonstrated that in vivo ED50 value of URB597, a major inhibitor of FAAH, was 66.4 µg/kg in rat brain. In conclusion, we proposed the calculated-k3 as an alternative index corresponding to regional FAAH concentrations and suggested that PET with [11C]DFMC enables occupancy study for new pharmaceuticals targeting FAAH.","subitem_description_type":"Abstract"}]},"item_8_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"ASPET"}]},"item_8_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1124/jpet.119.263772","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://pubmed.ncbi.nlm.nih.gov/32241809/","subitem_relation_type_select":"URI"}}]},"item_8_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0022-3565","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":"Yamasaki, Tomoteru"}],"nameIdentifiers":[{"nameIdentifier":"1027160","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ohya, Tomoyuki"}],"nameIdentifiers":[{"nameIdentifier":"1027161","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Mori, Wakana"}],"nameIdentifiers":[{"nameIdentifier":"1027162","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Yiding"}],"nameIdentifiers":[{"nameIdentifier":"1027163","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Wakizaka, Hidekatsu"}],"nameIdentifiers":[{"nameIdentifier":"1027164","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Nengaki, Nobuki"}],"nameIdentifiers":[{"nameIdentifier":"1027165","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Fujinaga, Masayuki"}],"nameIdentifiers":[{"nameIdentifier":"1027166","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kikuchi, Tatsuya"}],"nameIdentifiers":[{"nameIdentifier":"1027167","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ming-Rong, Zhang"}],"nameIdentifiers":[{"nameIdentifier":"1027168","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Tomoteru, Yamasaki","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1027169","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Tomoyuki, Ohya","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1027170","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Wakana, Mori","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1027171","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Yiding","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1027172","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hidekatsu, Wakizaka","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1027173","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Nobuki, Nengaki","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1027174","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Masayuki, Fujinaga","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1027175","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Tatsuya, Kikuchi","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1027176","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Ming-Rong","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1027177","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 an In Vivo Method to Estimate Effective Drug Doses and Quantify Fatty Acid Amide Hydrolase in Rodent Brain using Positron Emission Tomography Tracer N-(3,4-dimethylisoxazol-5-yl)piperazine-4-[4-(2-fluoro-4-[11C]methylphenyl)thiazol-2-yl]-1-carboxamide ([11C]DFMC)","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Development of an In Vivo Method to Estimate Effective Drug Doses and Quantify Fatty Acid Amide Hydrolase in Rodent Brain using Positron Emission Tomography Tracer N-(3,4-dimethylisoxazol-5-yl)piperazine-4-[4-(2-fluoro-4-[11C]methylphenyl)thiazol-2-yl]-1-carboxamide ([11C]DFMC)"}]},"item_type_id":"8","owner":"1","path":["1"],"pubdate":{"attribute_name":"公開日","attribute_value":"2020-04-10"},"publish_date":"2020-04-10","publish_status":"0","recid":"79840","relation_version_is_last":true,"title":["Development of an In Vivo Method to Estimate Effective Drug Doses and Quantify Fatty Acid Amide Hydrolase in Rodent Brain using Positron Emission Tomography Tracer N-(3,4-dimethylisoxazol-5-yl)piperazine-4-[4-(2-fluoro-4-[11C]methylphenyl)thiazol-2-yl]-1-carboxamide ([11C]DFMC)"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T17:56:31.828002+00:00"}