Astatine-211-Towards In Vivo Stable Astatine-211 Labeled Radiopharmaceuticals and Their (Pre)Clinical Applications

Targeted radioligand therapy has emerged as a promising treatment option for eradicating advanced cancer forms. α-Emitters are considered particularly promising as they can obliterate (micro)-metastases. The α-emitter astatine-211 (²¹¹At) has experienced increased interest due to its favorable decay properties. As a result, various ²¹¹At-astatination strategies have been developed to address challenges associated with working with this "halogenic metalloid." This review summarizes efforts to produce and scale ²¹¹At, describes its physicochemical properties, discusses the advantages and disadvantages of using a radionuclide with a half-life of 7.2 h and outlines procedures for astatinating radiopharmaceuticals. Moreover, a key focus of this review is to rationalize strategies aimed at minimizing in vivo deastatination. A brief overview of on-going (pre)clinical development with ²¹¹At-labeled radiopharmaceuticals is provided. Astatinated radiopharmaceuticals will play a pivotal role in cancer management in the near future when challenges related to scalability and in vivo stability have been addressed and clinical studies have shown the benefit of ²¹¹At compared to longer-lived therapeutic radionuclides.