{"created":"2023-05-15T14:52:32.375952+00:00","id":71732,"links":{},"metadata":{"_buckets":{"deposit":"1cfe8c8b-c96c-4bc1-b470-7c376cfcb89b"},"_deposit":{"created_by":1,"id":"71732","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"71732"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00071732","sets":["10:28"]},"author_link":["705949","705942","705943","705938","705947","705953","705956","705944","705946","705955","705957","705958","705951","705959","705940","705952","705945","705948","705950","705941","705954","705939"],"item_10005_date_7":{"attribute_name":"発表年月日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2015-05-28","subitem_date_issued_type":"Issued"}]},"item_10005_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Objectives: The indole-containing small molecule 1-methyl-tryptophan (1MTrp) is known as a specific inhibitor targeted immune checkpoint protein indoleamine-2,3-dioxygenase (IDO)- switching off the effector T cells of the immune system to support tumor growth. 1MTrp has shown attractive antitumor activity without noticeable toxicity [1], and its phase I trial had been completed in 2014. However, 1MTrp exists as 2 stereoisomers of L and D. Most preclinical studies have employed the racemic mixture, thus leaving a long-standing debate in immunology and oncology, which stereoisomers have the potential of immune checkpoint inhibitor [2,3]. To remove the blindfold of 1MTrp effects and guide its immunotherapy development, we synthesized 1-N-[11C]methyl]-L- and -D-tryptophan ([11C]L-1MTrp and [11C]D-1-MTrp) and compared their pharmacokinetics by PET.\nMethods: [11C]L-1MTrp and [11C]D-1MTrp were synthesized by reaction of the corresponding Boc-Trp-OEt with [11C]CH3I at 80 °C for 5 min, followed by deprotection with 2 N HCl at 100 °C for 5 min. Pharmacokinetics of the L and D isomers were compared by dynamic PET scans and biodistribution study following the injection of the radioprobes in rats. \nResults: [11C]L-1MTrp and [11C]D-1MTrp were obtained with radiochemical yields of 47.0 ± 6.3% (n = 80, based on [11C]CO2, EOS), radiochemical purity of > 98%, and specific activity of 47―130 GBq/μmol, showing high enantiomeric purity. PET imaging in rats revealed [11C]L-1MTrp had the highest accumulation of radioactivity (SUV 2.88 ± 0.03) in the pancreas with high IDO expression, while [11C]D-1MTrp showed the highest uptake (SUV 1.16 ± 0.03) in the kidney at 60 min after the radioprobes injection respectively. Ex vivo biodistribution results supported the PET images and indicated that uptake of L isomer in each organ was significantly higher than D isomer except in the kidney. Quite different tissue distribution was verified between the 2 stereoisomers. \nConclusions: Both [11C]L-1MTrp and [11C]D-1MTrp are useful PET probes for tracking the pharmacokinetics of 1MT in vivo. Imaging the immune checkpoint inhibitors would enable us to take a new look at cancer immunotherapy and drug development.\n\\nReference: [1].Muller AJ, et al. Nat Med. 2005;11:312. [2]. Hou DY, et al. Cancer Res. 2007;67:792. [3] Lob S, et al. Blood. 2008;111:2152.","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":"21st International Symposium on Radiopharmaceutical Sciences","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":"Kumata, Katsushi"}],"nameIdentifiers":[{"nameIdentifier":"705938","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Xie, Lin"}],"nameIdentifiers":[{"nameIdentifier":"705939","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Yui, Joji"}],"nameIdentifiers":[{"nameIdentifier":"705940","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hatori, Akiko"}],"nameIdentifiers":[{"nameIdentifier":"705941","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Yiding"}],"nameIdentifiers":[{"nameIdentifier":"705942","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Nengaki, Nobuki"}],"nameIdentifiers":[{"nameIdentifier":"705943","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Fujinaga, Masayuki"}],"nameIdentifiers":[{"nameIdentifier":"705944","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Yamasaki, Tomoteru"}],"nameIdentifiers":[{"nameIdentifier":"705945","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Shimoda, Yoko"}],"nameIdentifiers":[{"nameIdentifier":"705946","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Maeda, Jun"}],"nameIdentifiers":[{"nameIdentifier":"705947","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Ming-Rong"}],"nameIdentifiers":[{"nameIdentifier":"705948","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"熊田 勝志","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"705949","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"謝 琳","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"705950","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"由井 譲二","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"705951","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"羽鳥 晶子","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"705952","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"張 一鼎","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"705953","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"念垣 信樹","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"705954","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"藤永 雅之","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"705955","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"山崎 友照","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"705956","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"下田 陽子","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"705957","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"前田 純","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"705958","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"張 明栄","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"705959","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":"Radiosynthesis and pharmacokinetic comparison of 1-N-[11C]methyl]-L- and -D-tryptophan","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Radiosynthesis and pharmacokinetic comparison of 1-N-[11C]methyl]-L- and -D-tryptophan"}]},"item_type_id":"10005","owner":"1","path":["28"],"pubdate":{"attribute_name":"公開日","attribute_value":"2015-06-18"},"publish_date":"2015-06-18","publish_status":"0","recid":"71732","relation_version_is_last":true,"title":["Radiosynthesis and pharmacokinetic comparison of 1-N-[11C]methyl]-L- and -D-tryptophan"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T19:47:59.600973+00:00"}