学術雑誌論文

学術雑誌論文

text

Journal of Radioanalytical and Nuclear Chemistry. 2026

Radioactivity- and time-dependent cellular cytotoxicity of astatine-211-labeled FAP-targeting radiopharmaceuticals

Springer Nature

英語

text

2026-06-30

https://doi.org/10.1007/s10967-026-10999-6

Fibroblast activation protein (FAP), which is overexpressed in cancer-associated fibroblasts (CAFs) is an attractive stromal target for a-therapy. We previously reported moderate anti-tumor effects of ²¹¹At-labeled FAP inhibitors (FAPI) in a PANC-1 xenograft mouse model, where insufficient tumor accumulation and the absence of FAP expression in tumor cells limited therapeutic efficacy. In this study, we performed in vitro mechanistic follow-up experiments using FAP-negative PANC-1 cells to clarify the radioactivity–time-dependent cytotoxicity of ²¹¹At-labeled FAPI compared with free ²¹¹At (non-conjugated ²¹¹At). We found that, whereas free ²¹¹At showed only limited cytotoxicity, ²¹¹At-labeled FAPI exerted significant cytotoxic effects. Systematic variation of activity concentrations and exposure durations revealed that cytotoxicity depended primarily on sustained pericellular exposure rather than initial radioactivity levels. These findings provide mechanistic, hypothesis-generating insight into how CAF-targeted ²¹¹At radiopharmaceuticals can exert effective cytotoxicity without direct tumor cell targeting and may inform future optimization of stromal-targeted a-therapy, while further in vivo and translational studies will be required.

This article is licensed under a Creative Commons Attribution 4.0 International License.

106026

Radioactivity- and time-dependent cellular cytotoxicity of astatine-211-labeled FAP-targeting radiopharmaceuticals

Springer Nature

英語

2026-06-30

Journal of Radioanalytical and Nuclear Chemistry

https://doi.org/10.1007/s10967-026-10999-6

https://hdl.handle.net/11094/106026