Abstract
Six-transmembrane epithelial antigen of prostate-1 (STEAP1) is a relatively new 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 ~185 MBq/10mg of 89Zr-DFO-MSTP2109A. 89Zr-DFO-MSTP2109 PET/CT images obtained 4-7 days post-injection were compared to 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 was correlated with tumor uptake by PET imaging. Bone and/or soft tissue biopsies were evaluated. Results: No significant toxicity occurred. Excellent uptake was observed in bone and soft tissue disease. Median SUVmax 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 (one on repeat biopsy). Bayesian analysis resulted in a best estimate of 86% of histologically positive lesions being true positive on imaging (95% confidence interval of 75%-100%). There was no correlation between SUVmax tumor uptake and STEAP1 IHC, survival following ADC treatment, number of ADC treatment cycle, or change in PSA. 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.
- Copyright © 2019 by the Society of Nuclear Medicine and Molecular Imaging, Inc.