A Phase I/II Study for Analytic Validation of ⁸⁹Zr-J591 ImmunoPET as a Molecular Imaging Agent for Metastatic Prostate Cancer

Purpose: Standard imaging for assessing osseous metastases in advanced prostate cancer remains focused on altered bone metabolism and is inadequate for diagnostic, prognostic, or predictive purposes. We performed a first-in-human phase I/II study of ⁸⁹Zr- DFO-huJ591 (⁸⁹Zr-J591) PET/CT immunoscintigraphy to assess performance characteristics for detecting metastases compared with conventional imaging modalities (CIM) and pathology. Experimental Design: Fifty patients with progressive metastatic castration-resistant prostate cancers were injected with 5 mCi of ⁸⁹Zr-J591. Whole-body PET/CT scans were obtained, and images were analyzed for tumor visualization. Comparison was made to contemporaneously obtained bone scintigraphy and cross-sectional imaging on a lesion-by-lesion basis and with biopsies of metastatic sites. Results: Median standardized uptake value for ⁸⁹Zr-J591-positive bone lesions (n 491) was 8.9 and for soft-tissue lesions (n 90), it was 4.8 (P < 0.00003). ⁸⁹Zr-J591 detected 491 osseous sites compared with 339 by MDP and 90 soft-tissue lesions compared with 124 by computed tomography (CT). Compared with all CIMs combined, ⁸⁹Zr-J591 detected an additional 99 osseous sites. Forty-six lesions (21 bone and 25 soft tissue) were biopsied in 34 patients; 18 of 19 ⁸⁹Zr-J591-positive osseous sites and 14 of 16 ⁸⁹Zr-J591-positive soft tissue sites were positive for prostate cancer. The overall accuracy of ⁸⁹Zr-J591 was 95.2%(20 of 21) for osseous lesions and 60% (15 of 25) for soft-tissue lesions. Conclusions: ⁸⁹Zr-J591 imaging demonstrated superior targeting of bone lesions relative to CIMs. Targeting soft-tissue lesions was less optimal, although ⁸⁹Zr-J591 had similar accuracy as individual CIMs. This study will provide benchmark data for comparing performance of proposed prostate-specific membrane antigen (PSMA) targeting agents for prostate cancer.