Development of PSMA-Targeted Alpha Therapy Using [²¹¹At]PSMA-5

Astatine (²¹¹At) is an alpha-emitting nuclide with a 7.2-hour half-life that can be produced using a 30-MeV cyclotron. In recent years, the number of production sites worldwide has been increasing, attracting growing attention to ²¹¹At. We have developed a novel ²¹¹At-labeled PSMA-targeted agent ([²¹¹At]PSMA-5). After conducting preclinical evaluations of its antitumor efficacy and safety, we initiated a first-in-human, investigator-initiated clinical trial in patients with metastatic castration-resistant prostate cancer. To date, the drug has been administered to a total of nine patients, and we have reported high accumulation of [²¹¹At]PSMA-5 in recurrent and metastatic lesions. While further efforts are required for the social implementation of ²¹¹At-based targeted alpha therapy, including the establishment of a supply chain and the accumulation of additional clinical evidence, PSMA-targeted alpha therapy using ²¹¹At represents a promising treatment modality owing to its cyclotron-based production, sustainability, and clean decay characteristics.