Imaging patients with metastatic castration-resistant prostate cancer using (89)Zr-DFO-MSTP2109A anti-STEAP1 antibody Journal Article


Authors: Carrasquillo, J. A.; Fine, B. M.; Pandit-Taskar, N.; Larson, S. M.; Fleming, S. E.; Fox, J. J.; Cheal, S. M.; O'Donoghue, J. A.; Ruan, S.; Ragupathi, G.; Lyashchenko, S. K.; Humm, J. L.; Scher, H. I.; Gönen, M.; Williams, S. P.; Danila, D. C.; Morris, M. J.
Article Title: Imaging patients with metastatic castration-resistant prostate cancer using (89)Zr-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 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.
Keywords: prostate cancer; membrane antigen; dosimetry; antibody; therapy; positron; phase-i trial; j591; monoclonal-antibody; zr-89; steap1
Journal Title: Journal of Nuclear Medicine
Volume: 60
Issue: 11
ISSN: 0161-5505
Publisher: Society of Nuclear Medicine  
Date Published: 2019-11-01
Start Page: 1517
End Page: 1523
Language: English
ACCESSION: WOS:000493975400009
DOI: 10.2967/jnumed.118.222844
PROVIDER: wos
PMCID: PMC6836860
PUBMED: 31053681
Notes: Source: Wos
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MSK Authors
  1. Stephen E Fleming
    11 Fleming
  2. Josef J Fox
    54 Fox
  3. Michael Morris
    349 Morris
  4. Mithat Gonen
    778 Gonen
  5. Govindaswami Ragupathi
    136 Ragupathi
  6. John Laurence Humm
    366 Humm
  7. Shutian Ruan
    50 Ruan
  8. Steven M Larson
    878 Larson
  9. Sarah Marie Cheal
    28 Cheal
  10. Howard Scher
    976 Scher
  11. Daniel C Danila
    106 Danila