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

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 t...

Full description

Saved in:
Bibliographic Details
Published in:Clinical cancer research 2015-12, Vol.21 (23), p.5277-5285
Main Authors: Pandit-Taskar, Neeta, O'Donoghue, Joseph A, Durack, Jeremy C, Lyashchenko, Serge K, Cheal, Sarah M, Beylergil, Volkan, Lefkowitz, Robert A, Carrasquillo, Jorge A, Martinez, Danny F, Fung, Alex Mak, Solomon, Stephen B, Gönen, Mithat, Heller, Glenn, Loda, Massimo, Nanus, David M, Tagawa, Scott T, Feldman, Jarett L, Osborne, Joseph R, Lewis, Jason S, Reuter, Victor E, Weber, Wolfgang A, Bander, Neil H, Scher, Howard I, Larson, Steven M, Morris, Michael J
Format: Article
Language:English
Subjects:
Biomarkers, Tumor
Bone Neoplasms - diagnosis
Bone Neoplasms - 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
Soft Tissue Neoplasms - secondary
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. 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. 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. (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.
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.CCR-15-0552