A phase I/II study for analytic validation of 89Zr-J591 immunoPET as a molecular imaging agent for metastatic prostate cancer Journal Article

Authors: Pandit-Taskar, N.; O'Donoghue, J. A.; Durack, J. C.; Lyashchenko, S. K.; Cheal, S. M.; Beylergil, V.; Lefkowitz, R. A.; Carrasquillo, J. A.; Martinez, D. F.; Fung, A. M.; Solomon, S. B.; Gonen, M.; Heller, G.; Loda, M.; Nanus, D. M.; Tagawa, S. T.; Feldman, J. L.; Osborne, J. R.; Lewis, J. S.; Reuter, V. E.; Weber, W. A.; Bander, N. H.; Scher, H. I.; Larson, S. M.; Morris, M. J.
Article Title: A phase I/II study for analytic validation of 89Zr-J591 immunoPET as a molecular imaging agent for metastatic prostate cancer
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 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.
Keywords: fdg-pet; therapy; solid tumors; trial; positron-emission-tomography; localization; c-11-acetate; f-18-fdg; membrane; monoclonal-antibody j591; antigen-expression
Journal Title: Clinical Cancer Research
Volume: 21
Issue: 23
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2015-12-01
Start Page: 5277
End Page: 5285
Language: English
ACCESSION: WOS:000365603800013
DOI: 10.1158/1078-0432.ccr-15-0552
PMCID: PMC4668231
PUBMED: 26175541
Notes: Article -- Source: Wos
Citation Impact
MSK Authors
  1. Joseph R Osborne
    60 Osborne
  2. Glenn Heller
    353 Heller
  3. Michael Morris
    355 Morris
  4. Mithat Gonen
    782 Gonen
  5. Neil Harrison Bander
    40 Bander
  6. Stephen Solomon
    304 Solomon
  7. Jason S Lewis
    307 Lewis
  8. Steven M Larson
    878 Larson
  9. Victor Reuter
    1074 Reuter
  10. Sarah Marie Cheal
    28 Cheal
  11. Howard Scher
    979 Scher
  12. Jeremy Charles Durack
    95 Durack
  13. Wolfgang Andreas Weber
    166 Weber
  14. Jarett Lawrence Feldman
    11 Feldman