Recent Advances in Radioligand Therapy

Radioligand therapy (RLT) is a targeted molecular approach that couples the specificity of receptor-mediated binding with the cytotoxic effects of radionuclide emission to achieve selective tumor irradiation while limiting damage to healthy tissues. This review summarizes the key recent updates in RLT, highlighting the major clinical advances in prostate cancer and gastroenteropancreatic neuroendocrine tumors (GEP-NETs). In GEP-NETs, the α-emitting compound [212Pb]Pb-DOTAMTATE demonstrated durable responses and a favorable safety profile in patients who had previously [177Lu]Lu-DOTATATE-based RLT, marking an important step toward next-generation α-particle therapies. In prostate cancer, data from large randomized trials further defined the role of [177Lu]Lu-PSMA-617 across disease settings, including comparisons with docetaxel, combination therapy with androgen deprivation and androgen receptor pathway inhibitors (ARPI) and neoadjuvant use before stereotactic body radiotherapy. Early phase studies have investigated novel therapeutic concepts, such as α–β emitter combinations, poly(ADP-ribose) polymerase (PARP) inhibitor synergy and emerging non-PSMA targets such as ACP3. Collectively, these findings reflect a rapidly expanding field, where improved ligand design, new isotopes and combinations are driving RLT toward broader clinical integration and more personalized treatment strategies. PEER REVIEWED ARTICLE **Peer reviewers:** Prof. Dr Klaus Strobel, Department of Radiology and Nuclear Medicine, Luzerner Kantonsspital, University Teaching and Research Hospital, University of Lucerne, Lucerne, Switzerland. Dr Riccardo Laudicella, Nuclear Medicine, Department of Biomedical and Dental Sciences and Morpho-Functional Imaging, Messina University, Messina, Italy. Received on October 31, 2025; accepted after peer review on November 20, 2025; published online November 29, 2025.