Journal
JOURNAL OF NUCLEAR MEDICINE
Volume 60, Issue 11, Pages 1517-1523Publisher
SOC NUCLEAR MEDICINE INC
DOI: 10.2967/jnumed.118.222844
Keywords
STEAP1; Zr-89; antibody; positron; prostate cancer
Funding
- Ludwig Center for Cancer Immunotherapy
- NCI [P01 CA33049]
- NIH/NCI Cancer Center support [P30 CA008748]
- Genentech, Inc. (Roche Group)
- Bayer AG
- Sanofi
- Endoycte, Inc.
- Progenics Pharmaceuticals, Inc.
- Corcept Therapeutics, Inc.
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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 Zr-89-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 Zr-89-DFO-MSTP2109A. Zr-89-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 SUVmax was 20.6 in bone and 16.8 in soft tissue. Sixteen of 17 lesions biopsied were positive on Zr-89-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 SUVmax tumor uptake and STEAP1 immunohistochemistry, survival after ADC treatment, number of ADC treatment cycles, or change in prostate-specific antigen level. Conclusion: Zr-89-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.
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