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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 |
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| 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 | |||||
