2026-10-24 量子科学技術研究開発機構,日本医療研究開発機構
図１．子宮体部漿液性がん治療の現状と標的アルファ線治療
＜関連情報＞
- https://www.qst.go.jp/site/press/20261024.html
- https://jnm.snmjournals.org/content/early/2026/10/22/jnumed.126.273073
211At標識トラスツズマブを用いた標的α療法は、マウスの子宮漿液性癌におけるトラスツズマブ耐性を克服する Targeted α-Therapy with 211At-Labeled Trastuzumab Overcomes Trastuzumab Resistance in Uterine Serous Carcinoma in Mice
Huizi Keiko Li, Mayuka Anko, Kouji Banno, Kotaro Nagatsu and Sumitaka Hasegawa
Journal of Nuclear Medicine Published: October 2026
DOI:https://doi.org/10.2967/jnumed.126.273073
Abstract
Uterine serous carcinoma (USC) is an aggressive endometrial cancer frequently associated with human epidermal growth factor receptor type 2 (HER2) overexpression and poor prognosis. Although trastuzumab improves outcomes, resistance remains a major clinical problem. This study determined whether targeted α-therapy using 211At-labeled trastuzumab (211At-trastuzumab) can overcome trastuzumab resistance in HER2-positive USC. Methods: 211At-trastuzumab was synthesized, and its binding and cytotoxicity in HER2-positive USC cell lines were evaluated. Three trastuzumab-resistant peritoneal metastasis mouse models were established: intrinsic resistance, trastuzumab-induced resistance, and acquired resistance. After a single intravenous administration (1.85 MBq), therapeutic efficacy was assessed using bioluminescence imaging and biodistribution analysis. Results: 211At-trastuzumab showed specific binding to HER2-positive USC cells and significantly reduced cell viability relative to the controls. In vivo, tumor uptake reached 17.4 ± 1.9 %ID/g at 24 h. A single dose significantly suppressed tumor growth in all 3 resistant models: intrinsic, induced, and acquired resistance (P < 0.05 vs. controls). No severe toxicity was observed. Conclusion: 211At-trastuzumab demonstrates potent antitumor efficacy against trastuzumab-resistant HER2-positive USC in preclinical models. Targeted α-therapy may represent a promising strategy to overcome resistance to HER2-targeted therapy.
