Targeting the internal epitope of prostate-specific membrane antigen with (89)Zr-7E11 immuno-PET Journal Article

Authors: Ruggiero, A.; Holland, J. P.; Hudolin, T.; Shenker, L.; Koulova, A.; Bander, N. H.; Lewis, J. S.; Grimm, J.
Article Title: Targeting the internal epitope of prostate-specific membrane antigen with (89)Zr-7E11 immuno-PET
Abstract: The potential of the positron-emitting 89Zr has been recently investigated for the design of radioimmunoconjugates for immuno-PET. In this study, we report the preparation and in vivo evaluation of 89Zr- desferrioxamine B (DFO)-7E11, a novel 89Zr-labeled monoclonal antibody (mAb) construct for targeted imaging of prostate-specific membrane antigen (PSMA), a prototypical cell surface marker highly overexpressed in prostate cancer. The ability of 89Zr-DFO-7E11 to delineate tumor response to therapy was also investigated, because it binds to the intracellular epitope of PSMA, which becomes available only on membrane disruption in dead or dying cells. Methods: 7E11 as a marker of dying cells was studied by flow cytometry and microscopy of cells after antiandrogen-, radio-, and chemotherapy in LNCaP and PC3 PSMA-positive cells. The in vivo behavior of 89Zr-DFO-7E11 was characterized in mice bearing subcutaneous LNCaP (PSMA-positive) tumors by biodistribution studies and immuno-PET. The potential of assessing tumor response was evaluated in vivo after radiotherapy. Results: In vitro studies correlated 7E11 binding with markers of apoptosis (7-amino-actinomycin-D and caspase-3). In vivo biodistribution experiments revealed high, target-specific uptake of 89Zr-DFO-7E11 in LNCaP tumors after 24 h (20.35 ± 7.50 percentage injected dose per gram [%ID/g]), 48 h (22.82 ± 3.58%ID/g), 96 h (36.94 ± 6.27%ID/g), and 120 h (25.23 6 4.82%ID/g). Excellent image contrast was observed with immuno-PET. 7E11 uptake was statistically increased in irradiated versus control tumor as measured by immuno-PET and biodistribution studies. Binding specificity was assessed by effective blocking studies at 48 h. Conclusion: These findings suggest that 89Zr-DFO-7E11 displays high tumor-to-background tissue contrast in immuno-PET and can be used as a tool to monitor and quantify, with high specificity, tumor response in PSMA-positive prostate cancer. Copyright © 2011 by the Society of Nuclear Medicine, Inc.
Keywords: monoclonal antibodies; prostate cancer; pet; 89zr; 7e11; psma
Journal Title: Journal of Nuclear Medicine
Volume: 52
Issue: 10
ISSN: 0161-5505
Publisher: Society of Nuclear Medicine  
Date Published: 2011-10-01
Start Page: 1608
End Page: 1615
Language: English
DOI: 10.2967/jnumed.111.092098
PROVIDER: scopus
PUBMED: 21908391
PMCID: PMC3537833
Notes: --- - "Export Date: 2 November 2011" - "CODEN: JNMEA" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Neil Harrison Bander
    40 Bander
  2. Larissa Shenker
    17 Shenker
  3. Jason Philip Holland
    32 Holland
  4. Jan Grimm
    62 Grimm
  5. Jason S Lewis
    310 Lewis