WEKO3
アイテム
Utility of 211At-trastuzumab for the Treatment of Metastatic Gastric Cancer in the Liver: Evaluation of a Preclinical α-Radioimmunotherapy Approach in a Clinically-relevant Mouse Model
https://repo.qst.go.jp/records/81792
https://repo.qst.go.jp/records/8179205f999b9-5cd9-4711-87be-5579ab35eb72
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2021-02-06 | |||||
| タイトル | ||||||
| タイトル | Utility of 211At-trastuzumab for the Treatment of Metastatic Gastric Cancer in the Liver: Evaluation of a Preclinical α-Radioimmunotherapy Approach in a Clinically-relevant Mouse Model | |||||
| 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× Yukie, Morokoshi× Satoshi, Kodaira× Tamon, Kusumoto× Katsuyuki, Minegishi× Hiroaki, Kanda× Kotaro, Nagatsu× Sumitaka, Hasegawa× Li, Huizi× Satoshi, Kodaira× Tamon, Kusumoto× Katsuyuki, Minegishi× Kotaro, Nagatsu× Sumitaka, Hasegawa |
|||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | A liver metastasis from a primary gastric cancer (LMGC) is relatively common and results in an extremely poor prognosis due to a lack of effective therapeutics. We here demonstrate in a clinically-relevant mouse model that an α-radioimmunotherapy (α-RIT) approach with astatine-211-labeled-trastuzumab (211At-trastuzumab) has efficacy against LMGCs that are positive for human epidermal growth factor receptor 2 (HER2). Methods: 211At was produced in a cyclotron via a 209Bi (α, 2n) 211At reaction. 211At-trastuzumab was subsequently generated using a single-step labelling method. NCI-N87 cells (HER2-positive human GC cells) carrying a luciferase gene were intrasplenically transplanted into severe combined immunodeficiency mice to generate a HER2-positive LMGC model. A bio-distribution study was then conducted through the intravenous injection of 211At-trastuzumab (1 MBq) into these LMGC xenograft mice. In parallel with this experimental therapy, PBS, intact trastuzumab or 211At-non-specific human IgG (1MBq) were injected into control groups. The therapeutic efficacy was evaluated by monitoring tumor changes by chemiluminescence imaging. Monitoring of body weights, white blood cell counts, and serum markers of tissue damage were conducted at regular intervals. Microdosimetry using a CR39 plastic detector was also performed. Results: The biodistribution analysis revealed an increased uptake of 211At-trastuzumab in the metastasized tumors that reached approximately 12% of the injected dose per gram of tissue (%ID/g) at 24 hours. In contrast, its uptake to the surrounding liver was about 4%ID/g. The LMGCs in the mouse model reduced dramatically at 1 week after the single systemic injection of 211At-trastuzumab. No recurrences were observed in six of eight mice treated with this single injection and their survival time was significantly prolonged compared to the control groups, including the animals treated with 211At-non-specific antibodies. No severe toxicities or abnormalities in terms of body weight, white blood cell number, liver function, or kidney parameters were observed in the 211At-trastuzumab group. Microdosimetric studies further revealed that 211At-trastuzumab had been delivered at an 11.5- fold higher dose to the LMGC lesions compared to the normal liver. Conclusion: α-RIT with 211At-trastuzumab has considerable potential as an effective and safe therapeutic option for LMGC. | |||||
| 書誌情報 |
Journal of nuclear medicine 巻 62, 号 10, p. 1468-1474, 発行日 2021-02 |
|||||
| 出版者 | ||||||
| 出版者 | Society of Nuclear Medicine | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0161-5505 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.2967/jnumed.120.249300 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://jnm.snmjournals.org/content/early/2021/02/05/jnumed.120.249300.long | |||||
