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

• Published in: Acta biochimica et biophysica Sinica
• Main Authors: Zuo, Dashan, Wang, Hui, Yu, Boyi, Li, Qiang, Gan, Lu, Chen, Weiqiang
• Format: Journal Article
• Language: English
• Published: 26-11-2024
• ISSN: 1672-9145; 1745-7270; 1745-7270
• DOI: 10.3724/abbs.2024206

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.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.