{"created":"2023-05-15T14:59:23.917530+00:00","id":80587,"links":{},"metadata":{"_buckets":{"deposit":"0a104d4e-6daa-4fa6-b7bf-c066526e7867"},"_deposit":{"created_by":1,"id":"80587","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"80587"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00080587","sets":["1"]},"author_link":["1002329","1002326","1002325","1002322","1002328","1002327","1002331","1002323","1002330","1002324"],"item_8_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2020-06","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"12","bibliographicPageStart":"2914","bibliographicVolumeNumber":"25","bibliographic_titles":[{"bibliographic_title":"Molecules (Basel, Switzerland)"}]}]},"item_8_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Rociletinib (CO-1686), a 2,4-diaminopyrimidine derivative, is a highly potent tyrosine kinase inhibitor (TKI) that acts on epidermal growth factor receptor (EGFR) with L858R/T790M mutations. We supposed radioiodinated CO-1686 would function as a useful tool for monitoring EGFR L858R/T790M mutations. To aid in patient selection before therapy with EGFR-TKIs, this study aimed to develop a I-labeled derivative of CO-1686, -{3-[(2-{[4-(4-acetylpiperazin-1-yl)-2-methoxyphenyl]amino}-5-(trifluoromethyl)pyrimidine-4-yl] amino}-5-([I]iodophenyl)acrylamide ([I]ICO1686) and evaluate its selectivity toward EGFR L858R/T790M. Radiosynthesis was performed by iododestannylation of the corresponding tributylstannyl precursor with [I]NaI and -chlorosuccinimide. The selectivity of the tracer for detecting EGFR L858R/T790M was evaluated using three relevant non-small cell lung cancer (NSCLC) cell lines-H1975, H3255 and H441 overexpressing the dual mutation EGFR L858R/T790M, active mutant EGFR L858R and wild-type EGFR, respectively. The nonradioactive ICO1686 and the precursor compound were successfully synthesized. A novel radiolabeled probe, [I]ICO1686, was prepared with high radiochemical yield (77%) and purity (>99%). ICO1686 exhibited high cytotoxicity toward H1975 (IC 0.20 ± 0.05 μM) and H3255 (IC 0.50 ± 0.21 μM), which is comparable to that of CO-1686. In contrast, the cytotoxicity of ICO1686 toward H441 was 10-fold lower than that toward H1975. In the cell uptake study, the radioactivity uptake of [I]ICO1686 in H1975 was 101.52% dose/mg, whereas the uptakes in H3255 and H441 were 33.52 and 8.95% dose/mg, respectively. The uptake of [I]ICO1686 in H1975 was greatly reduced to 45.61% dose/mg protein by treatment with excess CO-1686. In vivo biodistribution study of the radiotracer found that its accumulation in H1975 tumor (1.77 ± 0.43% ID/g) was comparable to that in H3255 tumor (1.63 ± 0.23% ID/g) and the accumulation in H1975 tumor was not reduced by pretreatment with an excess dose of CO-1686. Although this radiotracer exhibited highly specific in vitro uptake in target cancer cells, structural modification is required to improve in vivo biodistribution.","subitem_description_type":"Abstract"}]},"item_8_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"MDPI"}]},"item_8_relation_13":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"32599930","subitem_relation_type_select":"PMID"}}]},"item_8_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"10.3390/molecules25122914","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://doi.org/10.3390/molecules25122914","subitem_relation_type_select":"DOI"}}]},"item_8_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"1420-3049","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":"Fawwaz, Muammar"}],"nameIdentifiers":[{"nameIdentifier":"1002322","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Mishiro, Kenji"}],"nameIdentifiers":[{"nameIdentifier":"1002323","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Nishii, Ryuichi"}],"nameIdentifiers":[{"nameIdentifier":"1002324","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Sawazaki, Izumi"}],"nameIdentifiers":[{"nameIdentifier":"1002325","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Shiba, Kazuhiro"}],"nameIdentifiers":[{"nameIdentifier":"1002326","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kinuya, Seigo"}],"nameIdentifiers":[{"nameIdentifier":"1002327","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ogawa, Kazuma"}],"nameIdentifiers":[{"nameIdentifier":"1002328","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ryuichi, Nishii","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1002329","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kazuhiro, Shiba","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1002330","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Seigo, Kinuya","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1002331","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 Fundamental Evaluation of Radioiodinated Rociletinib (CO-1686) as a Probe to Lung Cancer with L858R/T790M Mutations of Epidermal Growth Factor Receptor (EGFR)","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Synthesis and Fundamental Evaluation of Radioiodinated Rociletinib (CO-1686) as a Probe to Lung Cancer with L858R/T790M Mutations of Epidermal Growth Factor Receptor (EGFR)"}]},"item_type_id":"8","owner":"1","path":["1"],"pubdate":{"attribute_name":"公開日","attribute_value":"2020-09-30"},"publish_date":"2020-09-30","publish_status":"0","recid":"80587","relation_version_is_last":true,"title":["Synthesis and Fundamental Evaluation of Radioiodinated Rociletinib (CO-1686) as a Probe to Lung Cancer with L858R/T790M Mutations of Epidermal Growth Factor Receptor (EGFR)"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T19:34:26.908559+00:00"}