{"created":"2023-05-15T14:47:55.449057+00:00","id":65683,"links":{},"metadata":{"_buckets":{"deposit":"d935a063-1024-4aa7-8c57-2eca3b06bdf7"},"_deposit":{"created_by":1,"id":"65683","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"65683"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00065683","sets":["10:29"]},"author_link":["647031","647041","647032","647042","647033","647039","647040","647035","647038","647044","647030","647036","647037","647043","647034"],"item_10005_date_7":{"attribute_name":"発表年月日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2015-06-09","subitem_date_issued_type":"Issued"}]},"item_10005_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"64Cu-diacetyl-bis (N4-methylthiosemicarbazone) (64Cu-ATSM) is a promising theranostic agent targeting over-reduced condition under hypoxia in tumors. Clinical studies on diagnosis with radiolabeled Cu-ATSM are currently conducted worldwide, revealing its prognostic value. However, detailed characteristics of the region of high 64Cu-ATSM uptake remained unclear. Here, using human colon carcinoma HT-29 model, we investigated characteristics of 64Cu-ATSM uptake regions relating to tumor malignancy, such as up-regulation of DNA repair and concentration of CD133+ cancer stem cells, and developed a strategy to enhance 64Cu-ATSM internal radiotherapy efficacy by inhibiting DNA repair with co-administration of nucleic acid (NA) antagonists. Methods: Distribution of 64Cu-ATSM was examined in HT29 tumors, and the samples from regions identified as 64Cu-ATSM high- and low-uptake regions were used for characterization. Gene expression profile, NA incorporation (BrdU uptake), and CD133+ cell ratio were studied. For in vivo treatment study, 64Cu-ATSM (37 MBq) injection with or without co-administration of NA antagonists was tested and compared to 64Cu-ATSM alone (37 or 74 MBq). Results: Up-regulation of the pathways related to DNA repair along with BrdU uptake, and elevated CD133+ cell ratio were observed in 64Cu-ATSM high-uptake regions. In treatment study, 64Cu-ATSM showed dose-dependent inhibition of tumor growth, although 74 MBq showed significant toxicity. Co-administration of NA antagonists with 37 MBq 64Cu-ATSM showed greater tumor growth suppression than 74 MBq 64Cu-ATSM alone, without significant toxicity, and effectively reduced CD133+ cell ratio. Conclusions: 64Cu-ATSM accumulation was associated with tumor malignant characteristics and 64Cu-ATSM therapy with NA antagonists could be an effective approach to target these characteristics.","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":"The Society of Nuclear Medicine (SNM) annual meeting 2015","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":"Yoshii, Yukie"}],"nameIdentifiers":[{"nameIdentifier":"647030","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Furukawa, Takako"}],"nameIdentifiers":[{"nameIdentifier":"647031","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Matsumoto, Hiroki"}],"nameIdentifiers":[{"nameIdentifier":"647032","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Yoshimoto, Mitsuyoshi"}],"nameIdentifiers":[{"nameIdentifier":"647033","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Ming-Rong"}],"nameIdentifiers":[{"nameIdentifier":"647034","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kiyono, Yasushi"}],"nameIdentifiers":[{"nameIdentifier":"647035","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Fujibayashi, Yasuhisa"}],"nameIdentifiers":[{"nameIdentifier":"647036","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Saga, Tsuneo"}],"nameIdentifiers":[{"nameIdentifier":"647037","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"吉井 幸恵","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"647038","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"古川 高子","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"647039","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"松本 博樹","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"647040","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"吉本 光喜","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"647041","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"張 明栄","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"647042","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"藤林 康久","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"647043","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"佐賀 恒夫","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"647044","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":"64Cu-ATSM internal radiotherapy targeting tumor malignant regions: sensitization based on its biological characteristics","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"64Cu-ATSM internal radiotherapy targeting tumor malignant regions: sensitization based on its biological characteristics"}]},"item_type_id":"10005","owner":"1","path":["29"],"pubdate":{"attribute_name":"公開日","attribute_value":"2015-06-18"},"publish_date":"2015-06-18","publish_status":"0","recid":"65683","relation_version_is_last":true,"title":["64Cu-ATSM internal radiotherapy targeting tumor malignant regions: sensitization based on its biological characteristics"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T20:57:24.722740+00:00"}