Journal
CLINICAL CANCER RESEARCH
Volume 21, Issue 23, Pages 5277-5285Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-15-0552
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Funding
- Starr Cancer Consortium
- prostate cancer program of Memorial Sloan Kettering Cancer Center
- Center for Targeted Radioimmunotherapy and Theranostics of the Ludwig Center for Cancer Immunotherapy
- David H. Koch Foundation
- NIH [P30CA008748]
- Landy Research Fund
- Hascoe Charitable Foundation
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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 Zr-89-DFO-huJ591 (Zr-89-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 Zr-89-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 Zr-89-J591-positive bone lesions (n = 491) was 8.9 and for soft-tissue lesions (n = 90), it was 4.8 (P < 0.00003). Zr-89-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, Zr-89-J591 detected an additional 99 osseous sites. Forty-six lesions (21 bone and 25 soft tissue) were biopsied in 34 patients; 18 of 19 Zr-89-J591-positive osseous sites and 14 of 16 Zr-89-J591-positive soft tissue sites were positive for prostate cancer. The overall accuracy of Zr-89-J591 was 95.2%(20 of 21) for osseous lesions and 60% (15 of 25) for soft-tissue lesions. Conclusions: Zr-89-J591 imaging demonstrated superior targeting of bone lesions relative to CIMs. Targeting soft-tissue lesions was less optimal, although Zr-89-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. (C) 2015 AACR.
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