Imaging Patients with Metastatic Castration-Resistant Prostate Cancer Using 89Zr-DFO-MSTP2109A Anti-STEAP1 Antibody

Abstract

Six-transmembrane epithelial antigen of prostate-1 (STEAP1) is a relatively newly identified target in prostate cancer. We evaluated the ability of PET/CT with ⁸⁹Zr-DFO-MSTP2109A, an antibody that recognizes STEAP1, to detect lesions in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: Nineteen mCRPC patients were prospectively imaged using approximately 185 MBq/10 mg of ⁸⁹Zr-DFO-MSTP2109A. ⁸⁹Zr-DFO-MSTP2109A PET/CT images obtained 4-7 d after injection were compared with bone and CT scans. Uptake in lesions was measured. Fifteen patients were treated with an antibody-drug conjugate (ADC) based on MSTP2109A; ADC treatment-related data were correlated with tumor uptake by PET imaging. Bone or soft-tissue biopsy samples were evaluated. Results: No significant toxicity occurred. Excellent uptake was observed in bone and soft-tissue disease. Median SUV_max was 20.6 in bone and 16.8 in soft tissue. Sixteen of 17 lesions biopsied were positive on ⁸⁹Zr-DFO-MSTP2109A, and all sites were histologically positive (1 on repeat biopsy). Bayesian analysis resulted in a best estimate of 86% of histologically positive lesions being true-positive on imaging (95% confidence interval, 75%-100%). There was no correlation between SUV_max tumor uptake and STEAP1 immunohistochemistry, survival after ADC treatment, number of ADC treatment cycles, or change in prostate-specific antigen level. Conclusion:⁸⁹Zr-DFO-MSTP2109A is well tolerated and shows localization in mCRPC sites in bone and soft tissue. Given the high SUV in tumor and localization of a large number of lesions, this reagent warrants further exploration as a companion diagnostic in patients undergoing STEAP1-directed therapy.

Keywords: 89Zr; STEAP1; antibody; positron; prostate cancer.

FIGURE 1.

⁸⁹Zr-DFO-MSTP2109A maximum-intensity projections of selected patients with bone metastases of various extents. Images were acquired at 6 d after injection and are displayed at same gray scale with SUV_max of 10. Patients in upper panel (particularly patients 3 and 9) have extensive metastatic bone disease. Uptake in noninvolved bone is low and not definitely seen in projection images. Physiologic blood-pool activity was prominent soon after injection, and much less blood-pool activity is seen in late images in those with more extensive bony disease. Uptake in liver is partially reflective of blood-pool activity and parenchymal accumulation. Low-level uptake is also noted in kidneys, and variable uptake is noted in bowel (intraluminal), which probably represents route of excretion.

FIGURE 2.

⁸⁹Zr-DFO-MSTP2109A images of patient 13 obtained 6 d after injection. Images showed bone uptake in vertebral lesion (middle panel, midline arrow), in addition to uptake in left axillary node (middle panel arrow in left axilla) that was biopsy-proven metastatic disease. Left cervical nodal uptake (left panel, arrow) and retroperitoneal node (right panel, arrow) showed abnormal uptake. Although these were negative on concurrent CT, follow-up ¹⁸F-FDG scan showed mild uptake at these sites.

FIGURE 3.

Number of lesions identified on ⁸⁹Zr-DFO-MSTP2109A correlated negatively with clearance of radioactivity from blood pool. SUV_mean in blood was lower in patients with higher number of lesions when all 19 patients were considered (last scan, 4–8 d) (Pearson r = −0.78, P = 0.0001) or when patients were scanned on most common day, which was 6 d (n = 16) (Pearson r = −0.91, P < 0.0001).