Alpha and Beta Emitters in Translational Nuclear Medicine: Clinical Advances, Challenges, and Future Direction.

Radiopharmaceutical therapy (RPT) has emerged as a transformative modality in oncology, particularly for patients with metastatic or inoperable tumors. By leveraging molecularly targeted carriers conjugated to cytotoxic radionuclides, RPT enables precise delivery of ionizing radiation to tumor sites while minimizing off-target effects. Central to this approach are alpha (α) and beta (β) particle-emitting radionuclides. This review aims to provide a comprehensive overview of all clinically relevant alpha and beta emitters and incorporates the most recent advances from 2017-2025, offering a comprehensive and up-to-date perspective. Alpha and beta emitters hold significant promises for the future, especially in nuclear medicine, energy, and environmental monitoring. Medically, these emitters are at the forefront of targeted radiotherapy, offering new hope for cancer treatment. Alpha emitters such as Actinium-225 and Radium-223 are gaining attention for their high linear energy transfer, which allows them to effectively kill cancer cells while minimizing damage to surrounding healthy tissues. Beta emitters, including Lutetium-177 and Iodine-131, are already widely used for treating thyroid cancer, neuroendocrine tumors, and prostate cancer. They offer a longer range in tissue penetration than alpha particles, making them suitable for larger or more diffuse tumors. Alpha and beta emitters hold tremendous promise in targeted radiotherapy. However, current research is limited by an incomplete understanding of resistance pathways, insufficient long-term safety and efficacy data, and underdeveloped personalized treatment frameworks. As production technologies improve and safety protocols advance, these emitters will likely play an even more prominent role in both health care and scientific innovation.