Evaluation of Targeted Alpha Therapy Using [ 211 At]FAPI1 in Triple-Negative Breast Cancer Xenograft Models.

Autor: Abe, Kaori, Watabe, Tadashi, Kaneda-Nakashima, Kazuko, Shirakami, Yoshifumi, Kadonaga, Yuichiro, Naka, Sadahiro, Ooe, Kazuhiro, Toyoshima, Atsushi, Giesel, Frederik, Usui, Takeshi, Masunaga, Nanae, Mishima, Chieko, Tsukabe, Masami, Yoshinami, Tetsuhiro, Sota, Yoshiaki, Miyake, Tomohiro, Tanei, Tomonori, Shimoda, Masafumi, Shimazu, Kenzo
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Zdroj: International Journal of Molecular Sciences; Nov2024, Vol. 25 Issue 21, p11567, 12p
Abstrakt: Triple-negative breast cancer (TNBC) presents limited therapeutic options and is associated with poor prognosis. Early detection and the development of novel therapeutic agents are therefore imperative. Fibroblast activation protein (FAP) is a membrane protein expressed on cancer-associated fibroblasts (CAFs) that plays an essential role in TNBC proliferation, migration, and invasion. Consequently, it is hypothesized that the Astatine (211At)-labeled FAP inhibitor (FAPI) selectively exerts anti-tumor effects through alpha-particle emission. In this study, we aimed to assess its theranostic capabilities by integrating [18F]FAPI-74 PET imaging with targeted alpha therapy using [211At]FAPI1 in TNBC models. Mice xenografts were established by transplanting MDA-MB-231 and HT1080 cells (control). As a parallel diagnostic method, [18F]FAPI-74 was administered for PET imaging to validate FAP expression. A single dose of [211At]FAPI1 (1.04 ± 0.10 MBq) was administered to evaluate the therapeutic efficacy. [18F]FAPI-74 exhibited high accumulation in MDA-MB-231 xenografts, and FAP expression was pathologically confirmed via immunostaining. The group that received [211At]FAPI1 (n = 11) demonstrated a significantly enhanced anti-tumor effect compared with the control group (n = 7) (p = 0.002). In conclusion, [18F]FAPI-74 PET imaging was successfully used to diagnose FAP expression, and as [211At]FAPI1 showed promising therapeutic efficacy in TNBC models, it is expected to be a viable therapeutic option. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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