Zuo Dashan, Wang Hui, Yu Boyi, Li Qiang, Gan Lu, Chen Weiqiang
Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.
Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou 730000, China.
Acta Biochim Biophys Sin (Shanghai). 2024 Nov 25;57(3):327-343. 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 ( At) and actinium-225 ( Ac) 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 At-/ Ac-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 At-/ Ac-radiopharmaceuticals for future treatments.
核医学治疗为肿瘤治疗提供了一种很有前景的方法，因为放射性核素衰变过程中释放的能量会对肿瘤细胞造成不可修复的损伤。值得注意的是，α衰变具有更为显著的破坏潜力。通过将α核素与抗体或小分子抑制剂结合，靶向α治疗（TAT）可以增强肿瘤破坏，同时将毒副作用降至最低，这使得TAT成为一种越来越有吸引力的抗肿瘤策略。由于其特殊的物理化学性质和生物学效应，砹-211（At）和锕-225（Ac）已成为TAT中高效的药物。在本综述中，我们重点介绍了At-/Ac放射性药物的应用，特别是在特定肿瘤靶点中的应用，如前列腺癌中的前列腺特异性膜抗原（PSMA）、血液系统恶性肿瘤中的分化簇（CD）、卵巢癌中的人表皮生长因子受体2（HER2）以及神经内分泌肿瘤中的生长抑素受体（SSTR）。我们综合了临床前和临床试验的进展，以深入了解At-/Ac放射性药物在未来治疗中的潜在前景。
