{"created":"2023-05-15T15:03:53.958097+00:00","id":86452,"links":{},"metadata":{"_buckets":{"deposit":"9fd75787-93b7-4a1a-96ea-ce8cf4e18142"},"_deposit":{"created_by":1,"id":"86452","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"86452"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00086452","sets":["2"]},"author_link":["1055163","1055162","1055160","1055159","1055164","1055168","1055158","1055165","1055161","1055166","1055167"],"item_10003_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2022-06","bibliographicIssueDateType":"Issued"},"bibliographic_titles":[{"bibliographic_title":"Nuclear Medicine and Biology"}]}]},"item_10003_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Objectives: The orexin network mainly relies on two G protein-coupled receptors, orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R), and two neuropeptides, orexin-A (a 33 amino acid peptide) and orexin-B (a 28 amino acid peptide). Orexin-A is a non-selective neuropeptide binding both OX1R and OX2R with similar affinities, while orexin-B has a much higher selectivity towards OX2R against OX1R (> 10 fold). It has been found that OX2R plays a key role in motivation, arousal and sleep-wake regulation. Several OX2R ligands have been developed for OX2R PET imaging, but highly specific PET probes are still lacking. Herein we report [11C]1 and [11C]2 as novel and potential PET ligands for orexin 2 receptor imaging.\nMethods: Compounds 1 and 2 were synthesized according to patent literature WO2004033418. The phenolic precursors were prepared from demethylation of compounds 1 and 2. The radiosynthesis of [11C]1 and [11C]2 were conducted by 11C-methylation of phenolic precursors precursors with [11C]CH3I and Cs2CO3 as the base in DMF at 80 oC for 5 min. The in vitro autoradiography studies on Sprague Dawley rat brain slices was performed.\nResults: Compounds 1 was prepared starting from 2-methoxyaniline, which was treated with 3-methylpyridine-2-sulfonyl chloride to obtain N-(2-methoxyphenyl)-3-methylpyridine-2-sulfonamide in 21% yield. The resulting compound was coupled with methyl 2-bromoacetate in 45% yield and then hydrolyzed with NaOH to form carboxylic acid, which was coupled to N-benzylethanamine in the presence of HATU providing compound 1 in 2% overall yield over four steps. Compounds 2 was synthesized in a similar pathway and achieved in 20% overall yield over four steps. The phenolic precursors were prepared from demethylation of compounds 1 and 2 in 41% and 45% yields, respectively. The PET ligands [11C]1 and [11C]2 were prepared via reactions with [11C]CH3I and both achieved in more than 10% radiochemical yields (decay corrected). The radiochemical purities of these tracers were greater than 99%, and both [11C]1 and [11C]2 were stable in saline in 90 min. In in vitro autoradiography studies with [11C]1 and [11C]2, high radioactivity accumulation was observed in the hippocampus, and cortex. In blocking studies, EMPA (10 μM) rendered diminished radioactivity in OX2R-rich brain regions.\nConclusion: We have developed two novel PET ligand [11C]1 and [11C]2 for imaging OX2R. The PET ligands [11C]1 and [11C]2 were both prepared in more than 10% radiochemical yield (decay corrected). High radioactivity accumulation was observed in the hippocampus, and cortex in in vitro autoradiography studies with [11C]1 and [11C]2. These tracers will be evaluated in the PET imaging study for OX2R in rodents and the results will be reported in due course.","subitem_description_type":"Abstract"}]},"item_10003_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Elsevier Ltd."}]},"item_10003_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0969-8051","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":"Rong, Jian"}],"nameIdentifiers":[{"nameIdentifier":"1055158","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Tomoteru, Yamasaki"}],"nameIdentifiers":[{"nameIdentifier":"1055159","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhao, Chunyu"}],"nameIdentifiers":[{"nameIdentifier":"1055160","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Chen, Jiahui"}],"nameIdentifiers":[{"nameIdentifier":"1055161","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhiwei, Xiao"}],"nameIdentifiers":[{"nameIdentifier":"1055162","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Li, Yinlong"}],"nameIdentifiers":[{"nameIdentifier":"1055163","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Lee Collier, Thomas"}],"nameIdentifiers":[{"nameIdentifier":"1055164","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Ming-Rong"}],"nameIdentifiers":[{"nameIdentifier":"1055165","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Liang, Steven"}],"nameIdentifiers":[{"nameIdentifier":"1055166","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Tomoteru, Yamasaki","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1055167","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Ming-Rong","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1055168","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 paper","resourceuri":"http://purl.org/coar/resource_type/c_5794"}]},"item_title":"Synthesis and Evaluation of Novel PET Ligands for Imaging Orexin2 receptor (OX2R) ","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Synthesis and Evaluation of Novel PET Ligands for Imaging Orexin2 receptor (OX2R) "}]},"item_type_id":"10003","owner":"1","path":["2"],"pubdate":{"attribute_name":"公開日","attribute_value":"2022-06-08"},"publish_date":"2022-06-08","publish_status":"0","recid":"86452","relation_version_is_last":true,"title":["Synthesis and Evaluation of Novel PET Ligands for Imaging Orexin2 receptor (OX2R) "],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T16:57:57.901273+00:00"}