Imaging Patients with Metastatic Castration-Resistant Prostate Cancer Using⁸⁹Zr-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 89 Zr-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 89 Zr-DFO-MSTP2109A. 89 Zr-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 89 Zr-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: 89 Zr-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.

Improved image reconstruction of 89Zr-immunoPET studies using a Bayesian penalized likelihood reconstruction algorithm

“…There is thus an incentive to reduce administered activities. Our experience at MSKCC reflects this; initial 89 Zr-immunoPET studies featured administered activities of approximately 185 MBq (5 mCi) [ 9 , 11 – 13 ], while more recent work has used approximately 74 MBq (2 mCi) [ 4 , 5 , 14 ]. In other centers, even lower activities of approximately 37 MBq (1 mCi) [ 1 , 6 ] have been used.…”

Treating Prostate Cancer by Antibody–Drug Conjugates

“…Of note, imaging through anti-STEAP1 antibody 89Zr-DFO-MSTP2109A revealed high SUV in bone and soft tissue localization from prostate cancer [ 48 ]. Bayesian analysis estimated an 86% of histologically positive lesions being true-positive on imaging, without toxicities [ 48 ], opening the way to further investigations of anti-STEAP1 antibodies in the diagnostic setting.…”

Clinical significance of STEAP1 extracellular vesicles in prostate cancer

“…STEAP1 is readily expressed in prostate tumors and elevated in all stages of the disease [16]. Given its restricted expression in normal human tissues, STEAP1 has been proposed as a target for immunotherapy and for imaging of PCa [16][17][18]. Here, we isolated EVs and identified the presence of STEAP1-positive EVs in the plasma of healthy males and males with PCa.…”