{"created":"2023-05-15T15:01:19.812482+00:00","id":83201,"links":{},"metadata":{"_buckets":{"deposit":"0dcb6d1f-2239-4930-a0d9-282587597b8e"},"_deposit":{"created_by":1,"id":"83201","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"83201"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00083201","sets":["10:28"]},"author_link":["997352","997341","997345","997339","997350","997343","997346","997340","997336","997333","997351","997335","997347","997348","997344","997337","997334","997353","997342","997349","997338"],"item_10005_date_7":{"attribute_name":"発表年月日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2021-06-11","subitem_date_issued_type":"Issued"}]},"item_10005_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"We have successfully developed 64Cu-cyclam-RAFT-c(-RGDfK-)4 (64Cu-RaftRGD) as a multimeric RGD-based radiopeptide for specifically targeting the transmembrane cell adhesion receptor, alphaVbeta3 integrin (aVb3). Ovarian cancer peritoneal metastases (OCPMs) are a pathophysiologically heterogeneous group of tumors. Despite advances in surgical cytoreduction and drug development, the 5-year survival rate for OCPM patients remains as low as <30%. The aVb3 is overexpressed on tumoral neovessels and also on ovarian cancer cells and the radioisotope 64Cu has a suitable half-life (12.7 h) and multiple decay modes for both PET imaging and therapeutic irradiation. Hence, the present study aimed to evaluate the radiotheranostic potential of 64Cu-RaftRGD in clinically relevant aVb3-positive OCPM small animal models.  Methods: Athymic BALB/c nude mice with intraperitoneally inoculated ovarian carcinoma IGR-OV1 and NIH:OVCAR-3 cells were used as the OCPM small animal models, and their corresponding subcutaneous xenografts were used as a reference. 64Cu-RaftRGD was administered either intravenously or intraperitoneally to determine the optimal injection route. We performed intratumoral distribution (ITD) studies, PET/CT imaging and quantification, biodistribution assay and radiation dosimetry, and therapeutic efficacy and toxicity studies. Results: Intraperitoneal administration (i.p.) was shown to be the efficient route for targeting 64Cu-RaftRGD to OCPMs with excellent tumor penetration. The fluorescent surrogate Cy5.5-labeled RaftRGD and high-resolution multifluorescence imaging found that the ITD of 64Cu-RaftRGD was colocalized with CD31-stained microvessels and spatially distinct from but complementary to that of pimonidazole-stained hypoxia. 64Cu-RaftRGD (i.p.) PET visualized multiple OCPM deposits and ascites. The biodistribution study demonstrated an inverse correlation between the tumor size (1.2–17.2 mm) and tumor uptake levels (also absorbed doses). 64Cu-RaftRGD at a radiotherapeutic dose (148 MBq/0.357 nmol, i.p.) showed antitumor activities by inhibiting tumor cell proliferation and inducing apoptosis detected on day 3 after therapy, and significantly prolonged the survival of mice. The toxicity evaluation of 148 MBq/0.357 nmol i.p. 64Cu-RaftRGD in normal mice for 60 days after administration demonstrated negligible toxicity in hematology and hepatorenal functions. Conclusion: Our results demonstrate the all-in-one potential of the i.p. 64Cu-RaftRGD as a tumor penetrating radiodrug for PET imaging-guided radiotherapy of OCPMs by targeting both tumoral neovessels and cancerous cells, with negligible toxicity. We propose that further study of intra- and intertumoral heterogeneity of the radiodrug in relation to the tumor microenvironment may provide a basis for understanding the treatment limitation and facilitate a rational combination therapy design.","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":"SNMMI2021　Annual Meeting","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":"Zhao-Hui, Jin"}],"nameIdentifiers":[{"nameIdentifier":"997333","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Atsushi, Tsuji"}],"nameIdentifiers":[{"nameIdentifier":"997334","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Degardin, Melissa"}],"nameIdentifiers":[{"nameIdentifier":"997335","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Aya, Sugyo"}],"nameIdentifiers":[{"nameIdentifier":"997336","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Satoshi, Obara"}],"nameIdentifiers":[{"nameIdentifier":"997337","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hidekatsu, Wakizaka"}],"nameIdentifiers":[{"nameIdentifier":"997338","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kotaro, Nagatsu"}],"nameIdentifiers":[{"nameIdentifier":"997339","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kuan, Hu"}],"nameIdentifiers":[{"nameIdentifier":"997340","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Ming-Rong"}],"nameIdentifiers":[{"nameIdentifier":"997341","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Dumy, Pascal"}],"nameIdentifiers":[{"nameIdentifier":"997342","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Boturyn, Didier"}],"nameIdentifiers":[{"nameIdentifier":"997343","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Tatsuya, Higashi"}],"nameIdentifiers":[{"nameIdentifier":"997344","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhao-Hui, Jin","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"997345","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Atsushi, Tsuji","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"997346","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Aya, Sugyo","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"997347","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Satoshi, Obara","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"997348","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hidekatsu, Wakizaka","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"997349","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kotaro, Nagatsu","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"997350","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kuan, Hu","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"997351","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Ming-Rong","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"997352","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Tatsuya, Higashi","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"997353","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":"A radiotheranostic study for strategic treatment of ovarian cancer peritoneal metastases using the all-in-one multimeric radiopeptide 64Cu-cyclam-RAFT-c(-RGDfK-)4","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"A radiotheranostic study for strategic treatment of ovarian cancer peritoneal metastases using the all-in-one multimeric radiopeptide 64Cu-cyclam-RAFT-c(-RGDfK-)4"}]},"item_type_id":"10005","owner":"1","path":["28"],"pubdate":{"attribute_name":"公開日","attribute_value":"2021-08-11"},"publish_date":"2021-08-11","publish_status":"0","recid":"83201","relation_version_is_last":true,"title":["A radiotheranostic study for strategic treatment of ovarian cancer peritoneal metastases using the all-in-one multimeric radiopeptide 64Cu-cyclam-RAFT-c(-RGDfK-)4"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T19:53:47.170582+00:00"}