Multifunctional Clickable Reagents for Rapid Bioorthogonal Astatination and Radio-Crosslinking

In the past decade, several developments have expanded the chemical toolbox for astatination and the preparation of ²¹¹At-labeled radiopharmaceuticals. However, there is still a need for advanced methods for the synthesis of astatinated (bio)molecules to address challenges such as limited in vivo stability. Herein, we report the development of multifunctional ²¹¹At-labeled reagents that can be prepared by applying a modular and versatile click approach for rapid assembly. The introduction of tetrazines as bioorthogonal tags enables rapid radiolabeling and radio-crosslinking, which is demonstrated by steric shielding of ²¹¹At to significantly increase label stability in human blood plasma.