{"created":"2023-07-27T06:59:24.212295+00:00","id":58972,"links":{},"metadata":{"_buckets":{"deposit":"d5386c30-9255-4bdc-b3ea-3e419728e3e3"},"_deposit":{"created_by":18,"id":"58972","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"58972"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00058972","sets":["4200:1874:1875"]},"author_link":["78846","22513","87","91215","20554","85011","103764","103767","115","91214","43"],"item_4_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2020","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"12","bibliographicPageStart":"2914","bibliographicVolumeNumber":"25","bibliographic_titles":[{"bibliographic_title":"Molecules"}]}]},"item_4_creator_33":{"attribute_name":"著者別表示","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"三代, 憲司"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"柴, 和弘"}],"nameIdentifiers":[{},{},{},{}]},{"creatorNames":[{"creatorName":"絹谷, 清剛"}],"nameIdentifiers":[{},{},{},{}]},{"creatorNames":[{"creatorName":"小川, 数馬"}],"nameIdentifiers":[{},{},{},{}]}]},"item_4_description_21":{"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 125I-labeled derivative of CO-1686, N-{3-[(2-{[4-(4-acetylpiperazin-1-yl)-2-methoxyphenyl]amino}-5-(trifluoromethyl)pyrimidine-4-yl] amino}-5-([125I]iodophenyl)acrylamide ([125I]ICO1686) and evaluate its selectivity toward EGFR L858R/T790M. Radiosynthesis was performed by iododestannylation of the corresponding tributylstannyl precursor with [125I]NaI and N-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, [125I]ICO1686, was prepared with high radiochemical yield (77%) and purity (>99%). ICO1686 exhibited high cytotoxicity toward H1975 (IC50 0.20 ± 0.05 µM) and H3255 (IC50 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 [125I]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 [125I]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. © 2020 by the authors.","subitem_description_type":"Abstract"}]},"item_4_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","subitem_description_type":"Other"}]},"item_4_description_5":{"attribute_name":"提供者所属","attribute_value_mlt":[{"subitem_description":"金沢大学疾患モデル総合研究センター","subitem_description_type":"Other"}]},"item_4_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00065234","subitem_identifier_reg_type":"JaLC"}]},"item_4_publisher_17":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"MDPI AG"}]},"item_4_relation_12":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"10.3390/molecules25122914","subitem_relation_type_select":"DOI"}}]},"item_4_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"http://www.mdpi.com/journal/molecules"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"http://www.mdpi.com/journal/molecules","subitem_relation_type_select":"URI"}}]},"item_4_rights_23":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"Copyright ©  author, Published by the MDPI AG"}]},"item_4_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"1420-3049","subitem_source_identifier_type":"ISSN"}]},"item_4_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Fawwaz, Muammar"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Mishiro, Kenji"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"Nishii, Ryuichi"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Sawazaki, Izumi"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Shiba, Kazuhiro"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"Kinuya, Seigo"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"Ogawa, Kazuma"}],"nameIdentifiers":[{},{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2022-01-28"}],"displaytype":"detail","filename":"ME-PR-SHIBA-K-25-02914-v2.pdf","filesize":[{"value":"1.5 MB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"ME-PR-SHIBA-K-25-02914-v2.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/58972/files/ME-PR-SHIBA-K-25-02914-v2.pdf"},"version_id":"a9721d0d-a9e3-4229-b06d-cd04b28ab570"}]},"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":"4","owner":"18","path":["1875"],"pubdate":{"attribute_name":"公開日","attribute_value":"2022-01-28"},"publish_date":"2022-01-28","publish_status":"0","recid":"58972","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":"18","weko_shared_id":-1},"updated":"2023-07-27T10:17:52.236005+00:00"}