Scott T. Tagawa, MD, MS, Weill Cornell Medical College, New York Presbyterian Hospital, NY, discusses the results of a dose-escalation study of fractionated and multiple-dose 225Ac-J591 in progressive metastatic castration-resistant prostate cancer (mCRPC). 225Ac-J591 is a new form of prostate-specific membrane antigen-targeted radionuclide therapy (PSMA-TRT), which harnesses the monoclonal antibody J591 to drive prostate-specific membrane antigen (PSMA) targeted activity of the alpha emitter actinium 225 (225Ac). A single dose of 225Ac-J592, up to 93.3 KBq/kg, was found to be well tolerated and no maximal tolerated dose (MTD) was reached; most adverse events were restricted to grades I and II. Most patients demonstrated some prostate-specific antigen (PSA) decline, and the progression-free survival (PFS) was around 5 months. This study will pave the way for further trials of alternative 225Ac-J591 regimens and combination therapies. This interview took place at the American Society of Clinical Oncology (ASCO) 2021 virtual meeting.