A first-in-human trial of actinium-225-PSMA-CY313 reported manageable salivary toxicity alongside preliminary biochemical and radiographic responses in heavily pretreated metastatic castration-resistant prostate cancer. The study’s safety and early activity signals support continued development of targeted alpha therapy in PSMA-positive disease. For the nuclear medicine and prostate oncology pipeline, the early data emphasize a balance between dose-limiting adverse effects and meaningful PSA/radiographic outcomes in difficult-to-treat settings. —