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 (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.

Figure A

Uniform prior distribution (A1); beta (19, 2) distribution for the probability that a J591-positive site will be biopsy-positive, which reflects the information gleaned from the biopsied sites (A2); and beta-binomial (470, 19, 2) distribution for the number of biopsy-positive lesions among the non-biopsied J591-positive lesions (A3).

Figure 1

Patient with metastatic prostate cancer (PSA 90.9) with ⁸⁹Zr-J591-positive lesions that were not seen on MDP. Follow-up imaging showed POD on MDP. ⁸⁹Zr-J591 scan (A) showed uptake in multiple bone sites (arrows) that were not seen on concurrent FDG scan (B) or bone scan (C). A follow-up bone scan (D) showed uptake in the sites and was consistent with POD.

Figure 2

Patient with metastatic prostate cancer (PSA of 27.4). Baseline bone scan (A) and FDG PET (B) showed suspicious uptake in left femur distally (arrow); CT scan (C) showed sclerotic focus in the region. ⁸⁹Zr-J591 scan transaxial and fused images (D, E) did not show any suspicious uptake. Biopsy of the femoral lesion showed benign enchondroma.

Figure 3

Patient with metastatic prostate cancer (PSA of 4.1). Baseline bone scan (A) and FDG PET (B) showed no suspicious lesions. ⁸⁹Zr-J591 scan (C) showed uptake in T11 and L3 as seen on sagittal images (C) and transaxial image (D) (arrows). CT scan did not show any corresponding abnormality (E). Biopsy of T11 was positive for metastatic carcinoma.