Attempts to Improve the In vivo Stability of At-211 Labeled Agents

Recently, targeted α-therapy (TAT) that uses radiopharmaceuticals emitting α-particles has shown high therapeutic effectiveness and has attracted global attention. Astatine-211 (211At) is one of the α-emitters applicable to TAT, and 211At-labeled agents have been actively developed. However, many 211At-labeled agents suffer from the in vivo deastatination, which causes accumulation of free astatide ([211At]At−) in normal tissues, such as the stomach, thyroid, spleen, and lung. The mechanism of in vivo deastatination remains unclear, and no established strategy exists for producing highly stable 211At-labeled agents. To address this problem, we have developed a novel astatination method using a neopentyl glycol (NpG) scaffold. Initially, the stability of 211At-labeled NpG scaffold was demonstrated using a low-molecular-weight model compound. We conjugated the NpG scaffold with various low-, middle-, and high-molecular-weight targeting molecules to produce 211At-labeled agents. This review summarizes the applicability and usefulness of the NpG scaffold.