Ndlovu, HonestMokoala, Kgomotso M.G.Lawal, Ismaheel OpeyemiEmmett, LouiseSathekge, Mike Machaba2025-09-102025-09-102024-07Ndlovu, H., Mokoala, K.M.G., Lawal, I. et al 2024, 'Prostate-specific membrane antigen: alpha-labeled radiopharmaceuticals', PET Clinics, vol. 19, no. 3, pp. 371-388, doi : 10.1016/j.cpet.2024.03.003.1556-8598 (print)1879-9809 (online)10.1016/j.cpet.2024.03.003http://hdl.handle.net/2263/104272Novel prostate-specific membrane antigen (PSMA) ligands labeled with α-emitting radionuclides are sparking a growing interest in prostate cancer treatment. These targeted alpha therapies (TATs) have attractive physical properties that deem them effective in progressive metastatic castrate-resistant prostate cancer (mCRPC). Among the PSMA TAT radiopharmaceuticals, [225Ac]Ac-PSMA has been used extensively on a compassionate basis and is currently undergoing phase I trials. Notably, TAT has the potential to improve quality of life and has favorable antitumor activity and outcomes in multiple scenarios other than in mCRPC. In addition, resistance mechanisms to TAT may be amenable to combination therapies. KEY POINTS • The physical characteristics of α-particles allow for the better radiobiological efficiency of prostate-specific membrane antigen radiopharmaceuticals that emit α-particles. They have a position in the progressive metastatic castrate-resistant prostate cancer because of their direct and indirect cytotoxic effects on DNA and organelles through reactive oxygen species, bystander, and abscopal immune-mediated pathways. • Whether the metastatic prostate cancer is hormone-sensitive or castration-resistant, targeted-alpha therapy (TAT) has shown strong antitumor effectiveness, long-term survival, and an improvement in quality of life in patients at different stages of the disease. • The salivary glands are the dose-limiting organs. Salivary gland toxicity secondary to TAT may manifest with indirect clinical symptoms such as loss of appetite impacting on the quality of life. Various mitigatory measures have been partially effective in reducing its incidence.en© 2024 Elsevier Inc. All rights reserved. Notice : this is the author’s version of a work that was accepted for publication in PET Clinics. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. A definitive version was subsequently published in PET Clinics, vol. 19, no. 3, pp. 371-388, doi : 10.1016/j.cpet.2024.03.003.Prostate-specific membrane antigen (PSMA)Prostate cancerCastrate-resistant prostate cancer (CRPC)Targeted alpha therapy (TAT)Metastatic castrate-resistant prostate cancer (mCRPC)Postprint Article