Background: There is a pressing need for improved imaging biomarkers to identify disease distribution and response in both localized and advanced prostate cancer patients. PSMA-directed imaging is undergoing analytic and clinical validation for these contexts of use. IAB2M is an anti-PSMA recombinant minibody (Mb) derived from huJ591. We have previously reported on 28 pts imaged with IAB2M(Pandit-Taskar et al, SNM 2015). Here we report the lesion targeting and uptake (SUV) of the Mb and correlation with pathology of biopsied lesions on the full complement of the 38 pts examined in this trial. Methods: 38 pts with progressive metastatic PCa received escalating amounts of the Mb (16 pts at 10mg, 16 pts at 20mg, 6 pts at 50mg) in a phase I/IIa trial. All pts underwent standard imaging (SI) using CT, bone scintigraphy (BS), FDG PET, followed by imaging with 5 mCi of IAB2M. Whole body PET/CT scans were performed and evaluated for lesion targeting and SUVmax. Biopsy (bx) locations were selected by a consensus panel prioritized on the basis of: IAB2M & FDG positivity, IAB2M & FDG mismatch, and CT or BS positivity & any PET mismatch. Results: A total of 556 lesions (410 bone, 146 soft tissue) in 38 pts were detected by SI or IAB2M. In bone, IAB2M detected 344 lesions (83.9%), CT 209 (51%), BS 211 (51.5%), and FDG 109 (26.6%). For soft tissue, IAB2M detected 119 (81.5%), CT 83 (56.8%), and FDG 79 (54.1%). The SUV for bone lesions ranged from 2.1-60.4 for 10mg Mb, 1.7- 33 in 20mg Mb, and 2.3-17.5 in 50mg Mb. For soft tissue lesions, SUV range was 3.1-45.4, 2.1-20, and 1.9-13.8 respectively. 28 bxs (13 bone, 15 soft tissue) were obtained from 27 pts; 27 bxs were evaluable (1 was non-diagnostic). 20/27 (74.1%) bxs were pos for PCa; 20/24 (83.3%) IAB2M pos lesions were path pos and 3/3 (100%) IAB2M neg lesions were neg on path. All imaging and path correlated (true pos + true neg) in 23/27 (85.2%) bxs. Conclusions: PET imaging with IAB2M has demonstrated higher lesion detection when compared with SI. IAB2M’s high concordance with path suggests pos findings represent bx confirmed PCa. Further studies to examine biochemically recurrent prostate cancer are planned. Clinical trial information: NCT01923727