136 Background: J591 is a monoclonal antibody which selectively binds the external domain of PSMA with high affinity. Two phase I trials of radiolabeled-J591 have been published; two additional studies have been completed. 90Y is a beta-emitting particle optimal for tumor lesions 28-42 mm in size; 177Lu is best suited for lesions 1-3 mm in diameter [O'Donoghue J Nuc Med 1995]. Methods: With WCMC IRB approval, long-term follow-up of 4 clinical trials and the ongoing studies was analyzed. Prospectively collected data were supplemented with retrospective additions when necessary. Median survival (OS) was calculated by Kaplan- Meier methodology. Results: Between 10/00 and 7/10, 132 pts with metastatic CRPC received radiolabeled J591 (103 received 177Lu-J591, 29 90Y-J591) with a median follow-up of 68.5 months (mo). Median age 70.3 yrs; all progressed after multiple lines of hormonal therapy, 41.7% received prior chemo, 48.5% received post-J591 chemo. Median Halabi nomogram score for the group was 146 (range 97- 196). OS for the entire group was 16.7 mo [95% CI 13.8, 19.7]. 26 (19.7%) experienced > 30% PSA decline, with OS of 22.4 mo (vs 13.6 mo for those with any PSA increase, p=0.08; p=0.006 at phase II doses). Pts receiving 177Lu-J591 had more 30% PSA declines than 90Y-J591 (21.3% vs 6.9%, p=0.06). 37.9% had measurable disease; those who received 90Y-J591 were more likely to have measurable response than 177Lu-J591 [p=0.04]. All objective tumor responses also had significant PSA declines. Of 15 pts with baseline and follow-up CTC counts (CellSearch methodology), 12 (80%) became or remained favorable at follow-up; 3 became or remained unfavorable. Conclusions: Radiolabled J591 is tolerable and efficacious. As predicted based upon their physical properties, 177Lu-J591 appears more effective for lower volume disease, with objective responses in larger volume disease only with 90Y-J591. Current trials utilizing 177Lu-J591 focus on predictive biomarkers, dose fractionation to improve tolerance and efficacy, combination with chemotherapy, and “salvage radioimmunotherapy” to delay the onset of metastases in men with progressive biochemical (micrometastatic) disease best suitable for 177Lu-J591. [Table: see text]