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Preclinical evaluation of podoplanin-targeted alpha-radioimmunotherapy with the novel antibody NZ-16 for malignant mesothelioma
https://repo.qst.go.jp/records/84081
https://repo.qst.go.jp/records/84081e6dc74da-a443-40c9-9b92-c46eaa164cf7
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2021-07-06 | |||||
| タイトル | ||||||
| タイトル | Preclinical evaluation of podoplanin-targeted alpha-radioimmunotherapy with the novel antibody NZ-16 for malignant mesothelioma | |||||
| 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_6501 | |||||
| 資源タイプ | journal article | |||||
| 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 |
Hitomi, Sudo
× Hitomi, Sudo× Atsushi, Tsuji× Aya, Sugyo× K. Kaneko, Mika× Kato, Yukinari× Kotaro, Nagatsu× Hisashi, Suzuki× Tatsuya, Higashi× Hitomi, Sudo× Atsushi, Tsuji× Aya, Sugyo× Kotaro, Nagatsu× Hisashi, Suzuki× Tatsuya, Higashi |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Purpose This study aimed to evaluate the potential of podoplanin (PDPN)-targeted alpha-radiotherapy (RIT) for treating malignant mesothelioma. Methods A newly developed anti-PDPN antibody, NZ-16, and a previous anti-PDPN antibody, NZ-12, were assessed. The in vitro properties of radiolabeled antibodies were evaluated by cell binding and competitive inhibition assays using PDPN-expressing NCI-H226 (H226) mesothelioma cells. The biodistribution of 111In-labeled antibodies was studied in tumor-bearing mice. Tumor volumes and body weights of mice treated with 90Y- and 225Ac-labeled NZ-16 were measured for 56 days. The absorbed doses were estimated on the basis of the biodistribution data. Pathologic analysis of tumors and organs was conducted. Results The radiolabeled NZ-16 specifically bound to H226 cells with higher affinity than NZ-12. The biodistribution studies showed higher tumor uptake of radiolabeled NZ-16 compared with NZ-12. RIT with 225Ac-labeled NZ-16 (11.1 and 18.5 kBq) had a significantly higher antitumor effect than RIT with 90Y-labeled NZ-16 (3.7 MBq; P < 0.01). 225Ac-labeled NZ-16 induced more necrosis compared with 90Y-labeled NZ-16, but the Ki-67 index and apoptosis rate were similar. The estimated absorbed doses were expected to be tolerable in mice. Temporary body weight loss occurred, but recovered within several days. No visible damage to major organs was detected. Conclusion The novel anti-PDPN antibody NZ-16 was a more effective RIT agent than NZ-12. Radiolabeled NZ-16, especially 225Ac-labeled NZ-16, markedly suppressed tumor growth and prolonged survival without inducing severe adverse effects. RIT with radiolabeled NZ-16 is a promising therapeutic option for malignant mesothelioma. |
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| 書誌情報 |
Cells 巻 10, 号 10, p. 2503, 発行日 2021-09 |
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| 出版者 | ||||||
| 出版者 | MDPI | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 2073-4409 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.3390/cells10102503 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://www.mdpi.com/2073-4409/10/10/2503 | |||||
