Annotating STEAP1 regulation in prostate cancer with (89)Zr immuno-PET Journal Article

Authors: Doran, M. G.; Watson, P. A.; Cheal, S. M.; Spratt, D. E.; Wongvipat, J.; Steckler, J. M.; Carrasquillo, J. A.; Evans, M. J.; Lewis, J. S.
Article Title: Annotating STEAP1 regulation in prostate cancer with (89)Zr immuno-PET
Abstract: Antibodies and antibody-drug conjugates targeting the cell surface protein 6 transmembrane epithelial antigen of prostate 1 (STEAP1) are in early clinical development for the treatment of castration-resistant prostate cancer (PCa). In general, antigen expression directly affects the bioactivity of therapeutic antibodies, and the biologic regulation of STEAP1 is unusually complicated in PCa. Paradoxically, STEAP1 can be induced or repressed by the androgen receptor (AR) in different human PCa models, while also expressed in AR-null PCa. Consequently, there is an urgent need to translate diagnostic strategies to establish which regulatory mechanism predominates in patients to situate the appropriate therapy within standard of care therapies inhibiting AR. Methods: To this end, we prepared and evaluated 89Zr-labeled MSTP2109A (89Zr-2109A), a radiotracer for PET derived from a fully humanized monoclonal antibody to STEAP1 in preclinical PCa models. Results: 89Zr-2109A specifically localized to the STEAP1-positive human PCa models CWR22Pc, 22Rv1, and PC3. Moreover, 89Zr-2109A sensitively measured treatment-induced changes (∼66% decline) in STEAP1 expression in CWR22PC in vitro and in vivo, a model we showed to express STEAP1 in an AR-dependent manner. Conclusion: These findings highlight the ability of immuno-PET with 89Zr-2109A to detect acute changes in STEAP1 expression and argue for an expansion of ongoing efforts to image PCa patients with 89Zr-2109A to maximize the clinical benefit associated with antibodies or antibody-drug conjugates to STEAP1.
Keywords: protein expression; unclassified drug; human cell; nonhuman; positron emission tomography; protein localization; cell proliferation; mouse; animal tissue; cell viability; animal experiment; animal model; in vivo study; in vitro study; tumor xenograft; immunoreactivity; prostate cancer; isotope labeling; tissue distribution; membrane protein; radiopharmaceutical agent; androgen receptor; pet; pet scanner; degradation; human; male; article; 2109a zr 89; cell surface protein 6 transmembrane epithelial antigen of prostate 1
Journal Title: Journal of Nuclear Medicine
Volume: 55
Issue: 12
ISSN: 0161-5505
Publisher: Society of Nuclear Medicine  
Date Published: 2014-12-01
Start Page: 2045
End Page: 2049
Language: English
DOI: 10.2967/jnumed.114.145185
PROVIDER: scopus
PUBMED: 25453051
PMCID: PMC4410715
Notes: Export Date: 2 January 2015 -- Source: Scopus
Citation Impact
MSK Authors
  1. Michael John Evans
    22 Evans
  2. Philip A Watson
    23 Watson
  3. Jason S Lewis
    353 Lewis
  4. Sarah Marie Cheal
    37 Cheal
  5. Daniel Eidelberg Spratt
    98 Spratt
  6. Michael G. Doran
    17 Doran