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Locoregional therapy with α-emitting trastuzumab peritoneal metastasis of human epidermal growth factor receptor 2-positive gastric cancer in mice
https://repo.qst.go.jp/records/49316
https://repo.qst.go.jp/records/493161926d601-8ac8-4be4-8d2d-5fe98130419b
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2017-07-03 | |||||
| タイトル | ||||||
| タイトル | Locoregional therapy with α-emitting trastuzumab peritoneal metastasis of human epidermal growth factor receptor 2-positive gastric cancer in mice | |||||
| 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 |
Li, Huizi
× Li, Huizi× Morokoshi, Yukie× Nagatsu, Kotaro× Kamada, Tadashi× Hasegawa, Sumitaka× Li, Huizi× Yukie, Morokoshi× Kotaro, Nagatsu× Tadashi, Kamada× Sumitaka, Hasegawa |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Peritoneal metastasis of gastric cancer (PMGC) is incurable and thus has an extremely poor prognosis. We have found, however, that locoregionally administered trastuzumab armed with astatine-211 (211At-trastuzumab) is effective against human epidermal growth factor receptor 2 (HER2)-positive PMGC in a xenograft mouse model. We first observed that 211At-trastuzumab can specifically bind and effectively kill NCI-N87 (N87) cells, which are HER2-positive human metastatic GC cells, both in vitro and in s.c. tumors. We established a PMGC mouse model using N87 xenografts stably expressing luciferase to test a-particle radioimmunotherapy with 211At-trastuzumab against PMGC. Biodistribution analysis in this PMGC mouse model revealed that the i.p. administration of 211At-trastuzumab (1 MBq) was a more efficient means of delivery of 211At into metastatic tumors than i.v.injection; the maximum tumor uptake with i.p. administration was over 60% injected dose per gram of tissue (%ID/g) compared to approximately 18%ID/g with i.v. injection. Surprisingly, a single i.p. injection of 211At-trastuzumab (1 MBq) was sufficient to completely eradicate intraperitoneally disseminated HER2-positive GC xenografts in two of six treated mice by inducing DNA doublestrand breaks, and to drastically reduce the tumor burden in another three mice. No bodyweight loss, leukocytopenia, or significant biochemical changes in liver or kidney function were observed in the treatment group. Accordingly, locoregionally administered 211At-trastuzumab significantly prolonged the survival time of HER2-positive PMGC mice compared with control treatments. Our results provide a proof-of-concept demonstration that locoregional therapy with 211At-trastuzumab may offer a new treatment option for HER2-positive PMGC. |
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| 書誌情報 |
Cancer Science 巻 108, 号 8, p. 1648-1656, 発行日 2017-07 |
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| 出版者 | ||||||
| 出版者 | 日本癌学会 | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1347-9032 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 28514062 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1111/cas.13282 | |||||
