Enhancing the Stability of ²¹¹At Radiopharmaceuticals: Insights from Ortho-Substituent Strategies

Astatine-211 (²¹¹At) is a promising alpha-emitting radionuclide for targeted alpha therapy (TAT), delivering high linear energy transfer (LET) and a short radiation range, making it ideal for cancer treatment while minimizing damage to surrounding healthy tissue. This viewpoint highlights recent advancements in the development of astatine-211 compounds for TAT, with a focus on the role of neighboring substituents in enhancing in vivo stability. By mitigating deastatination, these structural modifications improve radiopharmaceutical integrity, paving the way for more effective and clinically viable ²¹¹At-based radiopharmaceuticals.