Unveiled Impact of ²¹¹At-Labeled Compounds' Ability to Form Halogen Bonds on Their In Vivo Stability

²¹¹At is a radionuclide of great interest in nuclear medicine for cancer therapy, provided it is firmly bound to an appropriate targeting agent. In recent years, original ²¹¹At-labeled compounds have shown promising in vivo stability, without the underlying logic being identified. Herein, molecular modeling (two-component relativistic density functional theory) is used to assess the hypothesis that the degradation mechanism(s), leading to the release of free ²¹¹At, is related to the ability of labeled compounds to form halogen-bond interactions involving astatine. We highlight inhibition phenomena at play for a variety of compounds, in line with observations of enhanced stability, paving the way for a potentially applicable strategy to access robust radiopharmaceuticals.