Substrate Study for Dihydroxyboryl Astatine Substitution Reaction with Fibroblast Activation Protein Inhibitor (FAPI)

The alpha-emitting radioisotope astatine-211 (At-211) is a potential candidate for targeted alpha therapy. For low toxic astatination of FAPI(s) with dihydroxyboryl group (B-FAPI), a dihydroxyboryl-astatine substitution reaction was developed without using any toxic reagents. We achieved efficient astatination with less than 10 mu g of B-FAPI, which is feasible in drug manufacturing conditions. Additionally, the FAPa selectivity and cell uptake of At-211-labeled FAPI(s) (At-211-FAPI) exhibited promising results for high antitumor efficacy.