A Review of Recent Alpha and Beta Emitters in Translational Nuclear Medicine

Introduction: 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, each offering unique physical characteristics and therapeutic profiles that can be tailored to tumor burden, radiosensitivity, and microenvironment. Clinical advancements, including FDA approvals of [177Lu ]Lu-vipivotide tetraxetan (Pluvicto) for prostate cancer and [177Lu]Lu-DOTATATE and [64Cu]Cu-DOTA-TATE (Detectnet) for neuroendocrine tumors, underscore the growing impact of RPT. Nevertheless, challenges such as supply constraints on alpha emitters, off-target toxicities, and the need for personalized dosimetry remain. Objective: Our goal here is to critically examine the mechanisms, clinical applications, and evolving landscape of α- and β-emitting radiotherapeutics, emphasizing emerging strategies, ongoing clinical trials, and the future potential of radiotheranostics in precision oncology. Methods: Using the PubMed database, we provide an overview of all clinically relevant alpha and beta emitters and incorporate the most recent advances from 2017 to 2025, offering a comprehensive and up-to-date perspective. Results: Since 2017, over 10 clinical trials have been registered for alpha or beta emitter therapy targeting various cancers in adult populations. 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, including lung cancer. 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. This makes them ideal for treating small clusters of cancer cells or micrometastases. 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. Conclusions: 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 healthcare and scientific innovation. Funding Support This work was supported by the Nemours Foundation, NIH/NIGMS under the grant number P20GM103446 (PI: Duncan), and NIH/NIBIB under the grant number EB032025. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.