Abstract | 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 (89)Zr-DFO-huJ591 ((89)Zr-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 (89)Zr-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 (89)Zr-J591-positive bone lesions (n = 491) was 8.9 and for soft-tissue lesions (n = 90), it was 4.8 (P < 0.00003). (89)Zr-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, (89)Zr-J591 detected an additional 99 osseous sites. Forty-six lesions (21 bone and 25 soft tissue) were biopsied in 34 patients; 18 of 19 (89)Zr-J591-positive osseous sites and 14 of 16 (89)Zr-J591-positive soft tissue sites were positive for prostate cancer. The overall accuracy of (89)Zr-J591 was 95.2% (20 of 21) for osseous lesions and 60% (15 of 25) for soft-tissue lesions. CONCLUSIONS: (89)Zr-J591 imaging demonstrated superior targeting of bone lesions relative to CIMs. Targeting soft-tissue lesions was less optimal, although (89)Zr-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.
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Authors | Neeta Pandit-Taskar, Joseph A O'Donoghue, Jeremy C Durack, Serge K Lyashchenko, Sarah M Cheal, Volkan Beylergil, Robert A Lefkowitz, Jorge A Carrasquillo, Danny F Martinez, Alex Mak Fung, Stephen B Solomon, Mithat Gönen, Glenn Heller, Massimo Loda, David M Nanus, Scott T Tagawa, Jarett L Feldman, Joseph R Osborne, Jason S Lewis, Victor E Reuter, Wolfgang A Weber, Neil H Bander, Howard I Scher, Steven M Larson, Michael J Morris |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 21
Issue 23
Pg. 5277-85
(Dec 01 2015)
ISSN: 1557-3265 [Electronic] United States |
PMID | 26175541
(Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | ©2015 American Association for Cancer Research. |
Chemical References |
- Biomarkers, Tumor
- Radiopharmaceuticals
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Topics |
- Biomarkers, Tumor
- Bone Neoplasms
(diagnosis, secondary)
- Humans
- Male
- Molecular Imaging
(methods)
- Neoplasm Metastasis
- Positron-Emission Tomography
(methods)
- Prostatic Neoplasms
(diagnosis)
- Prostatic Neoplasms, Castration-Resistant
(diagnosis)
- Radiopharmaceuticals
- Reproducibility of Results
- Sensitivity and Specificity
- Soft Tissue Neoplasms
(diagnosis, secondary)
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