WEKO3
アイテム
{"_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": ["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 \u003c30%. 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"], "permalink_uri": "https://repo.qst.go.jp/records/83201", "pubdate": {"attribute_name": "公開日", "attribute_value": "2021-08-11"}, "publish_date": "2021-08-11", "publish_status": "0", "recid": "83201", "relation": {}, "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_shared_id": -1}
A radiotheranostic study for strategic treatment of ovarian cancer peritoneal metastases using the all-in-one multimeric radiopeptide 64Cu-cyclam-RAFT-c(-RGDfK-)4
https://repo.qst.go.jp/records/83201
https://repo.qst.go.jp/records/832019e43690e-b4f7-4206-a900-ac99edff07b7
Item type | 会議発表用資料 / Presentation(1) | |||||
---|---|---|---|---|---|---|
公開日 | 2021-08-11 | |||||
タイトル | ||||||
タイトル | A radiotheranostic study for strategic treatment of ovarian cancer peritoneal metastases using the all-in-one multimeric radiopeptide 64Cu-cyclam-RAFT-c(-RGDfK-)4 | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
資源タイプ | conference object | |||||
アクセス権 | ||||||
アクセス権 | metadata only access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
著者 |
Zhao-Hui, Jin
× Zhao-Hui, Jin× Atsushi, Tsuji× Degardin, Melissa× Aya, Sugyo× Satoshi, Obara× Hidekatsu, Wakizaka× Kotaro, Nagatsu× Kuan, Hu× Zhang, Ming-Rong× Dumy, Pascal× Boturyn, Didier× Tatsuya, Higashi× Zhao-Hui, Jin× Atsushi, Tsuji× Aya, Sugyo× Satoshi, Obara× Hidekatsu, Wakizaka× Kotaro, Nagatsu× Kuan, Hu× Zhang, Ming-Rong× Tatsuya, Higashi |
|||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | 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. | |||||
会議概要(会議名, 開催地, 会期, 主催者等) | ||||||
内容記述タイプ | Other | |||||
内容記述 | SNMMI2021 Annual Meeting | |||||
発表年月日 | ||||||
日付 | 2021-06-11 | |||||
日付タイプ | Issued |