{"created":"2023-05-15T15:02:46.494759+00:00","id":85109,"links":{},"metadata":{"_buckets":{"deposit":"5af26728-d8ac-4c09-a197-ce8fede3fbe9"},"_deposit":{"created_by":1,"id":"85109","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"85109"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00085109","sets":["1"]},"author_link":["1026134","1026142","1026143","1026138","1026129","1026139","1026144","1026137","1026131","1026133","1026145","1026135","1026136","1026130","1026141","1026140","1026132"],"item_8_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2022-02","bibliographicIssueDateType":"Issued"},"bibliographicPageEnd":"15","bibliographicPageStart":"10","bibliographicVolumeNumber":"108-109","bibliographic_titles":[{"bibliographic_title":"Nuclear Medicine and Biology"}]}]},"item_8_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Background: [64Cu]Cu-diacethyl-bis(N4-methylthiosemicarbazone) ([64Cu]Cu-ATSM) is a radioactive hypoxia-targeting therapeutic agent, and the efficacy and safety of [64Cu]Cu-ATSM in the treatment of malignant brain tumors are evaluated in clinical trials. For the clinical application of [64Cu]Cu-ATSM, we determined a drug formulation incorporating a stabilizer against radiolysis and confirmed its radiochemical stability. This study aimed to identify trace chemical impurities derived from the degradation of ATSM contained in the [64Cu]Cu-ATSM investigational drug formulation and assess their potential hazards by quantitative structure–activity relationship (QSAR) assessment.\nMethods: We hypothesized that the chemical impurities contained in the [64Cu]Cu-ATSM formulation were derived from the degradation of ATSM. Therefore, we first identified the degradants of ATSM using LC-MS/MS. ATSM was dissolved with the drug formulation of [64Cu]Cu-ATSM, except for 64Cu, and analyzed by LC-MS/MS at 0 and 48 h after sample preparation. Subsequently, the chemical impurities contained in the [64Cu]Cu-ATSM formulation were measured at 0, 5, and 24 h after preparation by HPLC, and the results were compared to the degradants of ATSM. The potential hazards of the chemical impurities contained in the [64Cu]Cu-ATSM formulation were assessed using the QSAR Toolbox (ver. 4.3). \nResults: Six ATSM degradants were detected and identified by LC-MS/MS analysis, indicating that the functional groups around the nitrogen and sulfur atoms of ATSM were affected. The same peaks were detected as trace chemical impurities in the [64Cu]Cu-ATSM formulation at 24 h, while no apparent peaks were detected at 0 and 5 h. The estimated LD50 values of these chemical impurities showed 4.31 mg/kg or more by QSAR assessment. In contrast, the estimated amount of each chemical impurity exposed to patients was 31.8 ng/kg or less per dose. The smallest margin between the amount of chemical impurities and smallest estimated LD50 value of the corresponding impurity was a ratio of approximately 1:700,000.\nConclusions: We identified trace chemical impurities derived from ATSM in the [64Cu]Cu-ATSM formulation. This suggests that the potential risk of the systemic exposure of patients to these chemical impurities is substantially low.","subitem_description_type":"Abstract"}]},"item_8_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Elsevier "}]},"item_8_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1016/j.nucmedbio.2022.02.001","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://www.sciencedirect.com/science/article/pii/S0969805122000129","subitem_relation_type_select":"URI"}}]},"item_8_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":"Chika, Igarashi"}],"nameIdentifiers":[{"nameIdentifier":"1026129","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hiroki, Matsumoto"}],"nameIdentifiers":[{"nameIdentifier":"1026130","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Masashi, Takahashi"}],"nameIdentifiers":[{"nameIdentifier":"1026131","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Fukiko, Hihara"}],"nameIdentifiers":[{"nameIdentifier":"1026132","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Tomoko, Tachibana"}],"nameIdentifiers":[{"nameIdentifier":"1026133","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Ming-Rong"}],"nameIdentifiers":[{"nameIdentifier":"1026134","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hiroaki, Kurihara"}],"nameIdentifiers":[{"nameIdentifier":"1026135","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Tatsuya, Higashi"}],"nameIdentifiers":[{"nameIdentifier":"1026136","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Yukie, Yoshii"}],"nameIdentifiers":[{"nameIdentifier":"1026137","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Chika, Igarashi","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1026138","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hiroki, Matsumoto","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1026139","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Masashi, Takahashi","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1026140","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Fukiko, Hihara","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1026141","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Tomoko, Tachibana","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1026142","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Ming-Rong","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1026143","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Tatsuya, Higashi","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1026144","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Yukie, Yoshii","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1026145","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":"Identification and quantitative structure–activity relationship assessment of trace chemical impurities contained in the therapeutic formulation of [64Cu]Cu-ATSM","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Identification and quantitative structure–activity relationship assessment of trace chemical impurities contained in the therapeutic formulation of [64Cu]Cu-ATSM"}]},"item_type_id":"8","owner":"1","path":["1"],"pubdate":{"attribute_name":"公開日","attribute_value":"2021-12-03"},"publish_date":"2021-12-03","publish_status":"0","recid":"85109","relation_version_is_last":true,"title":["Identification and quantitative structure–activity relationship assessment of trace chemical impurities contained in the therapeutic formulation of [64Cu]Cu-ATSM"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T18:00:01.761878+00:00"}