Tagawa ST, Vallabhajosula S, Christos PJ, et al. - In view of the efficacy and dose-response/toxicity data of lutetium-177–labeled anti-prostate-specific membrane antigen (PSMA) monoclonal antibody J591 (¹⁷⁷Lu-J591) that targets prostate cancer when delivered as a single dose, researchers examined if dose fractionation may facilitate administration of higher doses. Initial phase 1b dose-escalation cohorts comprised men with metastatic castration-resistant prostate cancer refractory to or refusing standard treatment options with normal neutrophil and platelet counts; this was followed by phase 2a cohorts treated at recommended phase 2 doses comprising 2 fractionated doses of ¹⁷⁷Lu-J591 2 weeks apart. They performed ¹⁷⁷Lu-J591 imaging after treatment, but performed no selection for PSMA expression before enrollment. Circulating tumor cell counts were estimated before and after treatment in phase 2 patients. Fractionated doses of ¹⁷⁷Lu-J591 ranging from 20 to 45 mCi/m² ×2, 2 weeks apart, were administered to 49 men. Outcomes suggest that higher cumulative radiation dosing could be achieved with fractionated administration of ¹⁷⁷Lu-J591. Higher doses resulted in decreased frequency and depth of PSA and an increase in overall survival, and toxicity (dose-limiting myelosuppression).