Astatine-211 and actinium-225: two promising nuclides in targeted alpha therapy

Nuclear medicine therapy offers a promising approach for tumor treatment, as the energy emitted during radionuclide decay causes irreparable damage to tumor cells. Notably, α-decay exhibits an even more significant destructive potential. By conjugating α-nuclides with antibodies or small-molecule inhibitors, targeted alpha therapy (TAT) can enhance tumor destruction while minimizing toxic side effects, making TAT an increasingly attractive antineoplastic strategy. Astatine-211 ( ²¹¹At) and actinium-225 ( ²²⁵Ac) have emerged as highly effective agents in TAT due to their exceptional physicochemical properties and biological effects. In this review, we highlight the applications of ²¹¹At-/ ²²⁵Ac-radiopharmaceuticals, particularly in specific tumor targets, such as prostate-specific membrane antigen (PSMA) in prostate cancers, cluster of differentiation (CD) in hematological malignancies, human epidermal growth factor receptor-2 (HER2) in ovarian cancers, and somatostatin receptor (SSTR) in neuroendocrine tumors. We synthesize the progress from preclinical and clinical trials to provide insights into the promising potential of ²¹¹At-/ ²²⁵Ac-radiopharmaceuticals for future treatments.