Recent advances in understanding and improving the stability of ²¹¹At-radiopharmaceuticals

Astatine-211 is more than ever a serious candidate radionuclide to achieve success of targeted alpha therapy of cancers in the close future. However, several challenges remain to be overcome in order to guarantee the translation of ²¹¹At-labeled radiopharmaceuticals to the clinic. Particularly, the lack of biological stability of ²¹¹At-labeling, which has been identified in early studies with astatoaryl-based compounds, is still the object of active research. This has led to two main approaches to optimize stability: i) modulation of the astatoaryl moiety, ii) binding astatine to other moieties than phenyl derivatives. In addition, improvement of the knowledge on astatine chemical properties now facilitates the design of optimal structures and opens new perspectives. Hypotheses have also emerged, rationalizing the potential mechanisms at stake in the in vivo degradation of the carbon‑astatine bond and that should facilitate the development of strategies to counter these events. In this work, we discuss the advances made in the stabilization of ²¹¹At-labeling since the last review dedicated to this topic reported by D.S. Wilbur in 2008.