EGFR-targeted ImmunoPET of UMUC3 orthotopic bladder tumors Journal Article


Authors: Hoang, T. T.; Mandleywala, K.; Viray, T.; Tan, K. V.; Lewis, J. S.; Pereira, P. M. R.
Article Title: EGFR-targeted ImmunoPET of UMUC3 orthotopic bladder tumors
Abstract: Purpose: Immuno-positron emission tomography (immunoPET) combines the specificity of an antibody with the sensitivity of PET to image dysregulated pathways in cancer. This study examines the performance of immunoPET using the radioimmunoconjugate [89Zr]Zr-DFO-Panitumumab to detect epidermal growth factor receptor (EGFR) expression in an orthotopic model of bladder cancer (BCa). Procedures: Expression and quantification of EGFR receptors were confirmed in four different BCa cell lines. Binding assays validated [89Zr]Zr-DFO-Panitumumab specificity for EGFR-expressing UMUC3 BCa cells. Subcutaneous and orthotopic UMUC3 xenografts were then used for PET imaging and ex vivo biodistribution of the radioimmunoconjugate. Control cohorts included non-tumor mice, 89Zr-labeled non-specific IgG, and blocking experiments. Results: [89Zr]Zr-DFO-Panitumumab binds specifically to EGFR-expressing UMUC3 cells with a Bmax value of 5.9 × 104 EGFRs/cell in vitro. ImmunoPET/CT images show localization of the antibody in subcutaneous UMUC3 xenografts and murine bladder tumors. In the orthotopic model, the immunoPET signal correlates with the respective tumor volume. Ex vivo biodistribution analysis further confirmed imaging results. Conclusion: The preclinical data presents a proof of concept for utilizing EGFR-targeted immunoPET to image BCa with altered EGFR protein levels. © 2022, World Molecular Imaging Society.
Keywords: positron emission tomography; mouse; animal; metabolism; animals; mice; epidermal growth factor receptor; cell line, tumor; diagnostic imaging; bladder cancer; bladder tumor; urinary bladder neoplasms; panitumumab; tissue distribution; tumor cell line; positron-emission tomography; egfr; zirconium; egfr protein, human; immunopet; antibody conjugate; immunoconjugates; procedures; erbb receptors; humans; human
Journal Title: Molecular Imaging and Biology
Volume: 24
Issue: 4
ISSN: 1536-1632
Publisher: Springer  
Date Published: 2022-08-01
Start Page: 511
End Page: 518
Language: English
DOI: 10.1007/s11307-022-01708-2
PUBMED: 35147837
PROVIDER: scopus
PMCID: PMC10187976
DOI/URL:
Notes: Article -- Export Date: 1 August 2022 -- Source: Scopus
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  1. Jason S Lewis
    456 Lewis
  2. Tara Viray
    12 Viray
  3. Tran Tu Hoang
    6 Hoang
  4. Kel Vin Tan
    1 Tan