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 89Zr-DFO-huJ591 (89Zr-J591) PET/CT immunoscintigraphy to assess performance characteristics for detecting metastases compared to conventional imaging modalities (CIMs) 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; soft tissue lesions (n = 90): 4.8 (p < .00003). 89Zr-J591 detected 491 osseous sites compared to 339 by MDP, and 90 soft tissue lesions compared to 124 by CT. Compared to all CIMs combined, 89Zr-J591 detected an additional 99 osseous sites. Forty-six lesions (21 bone, 25 soft tissue) were biopsied in 34 patients; 18/19 89Zr-J591-positive osseous sites and 14/16 89Zr-J591-positive soft tissue sites were positive for prostate cancer. The overall accuracy of 89Zr-J591 was 95.2% (20/21) for osseous lesions and 60% (15/25) 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 PSMA targeting agents for prostate cancer.

Evaluation of Castration-Resistant Prostate Cancer with Androgen Receptor–Axis Imaging

“…A follow-up analysis of lesion targeting in 50 patients with CRPC imaged using 89 Zr-J591 PET/CT showed good localization of both bone and soft-tissue lesions (46). Higher targeting, including both uptake and lesion detection, was seen for bone lesions than for softtissue lesions.…”

“…Bayesian analysis was used to predict the number of positive lesions among the unbiopsied sites for each modality separately for bone and soft tissue (46). The results showed the highest predicted number of positive findings for J591 in osseous lesions, as compared with other conventional modalities (Supplemental Table 1).…”

Anatomic and functional imaging in the diagnosis of spine metastases and response assessment after spine radiosurgery

“…Prostatespecific membrane antigen (PSMA) agents for prostate cancer, such as 89 Zr-J591, outperformed conventional imaging modalities including bone scan and CT in the initial detection of osseous prostate cancer lesions in patients. 34 Unfortunately, many of these tumor-specific agents remain largely investigational, and much like other antigenspecific compounds, they may be limited by tumoral heterogeneity. Although nuclear medicine techniques allow whole-body imaging, the special considerations of each technique and cost/availability must be accounted for when using imaging.…”

Molecular Imaging and Targeted Radionuclide Therapy of Prostate Cancer

“…Additionally, sensitivity and specificity can be estimated from biopsies of a limited number of lesions by Bayesian analysis (10). This method has not been commonly used so far but merits further investigation in metastatic prostate cancer because many patients present with multiple lesions and it becomes impossible to validate imaging findings for each of these lesions.…”

“…This method has not been commonly used so far but merits further investigation in metastatic prostate cancer because many patients present with multiple lesions and it becomes impossible to validate imaging findings for each of these lesions. By performing biopsies of discrepant lesions, one can also use Bayesian analysis as a potentially powerful approach for comparing two imaging tests (10).…”