@article{a5a89196e1cc4e8f978a1f7ecd351159,
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.",
keywords = "Bladder Cancer, EGFR, ImmunoPET",
author = "Hoang, {Tran T.} and Komal Mandleywala and Tara Viray and Tan, {Kel Vin} and Lewis, {Jason S.} and Pereira, {Patricia M.R.}",
note = "Funding Information: The authors acknowledge the Radiochemistry and Molecular Imaging Probe Core, supported by NIH grant P30 CA08748. This study was supported in part by the Geoffrey Beene Cancer Research Center of MSKCC, NIH NCI R35 CA232130, NIH R01 CA244233-01A1. We gratefully acknowledge Mr. William H. and Mrs. Alice Goodwin and the Commonwealth Foundation for Cancer Research and The Center for Experimental Therapeutics of MSKCC. P.M.R. Pereira acknowledges the Tow Foundation Postdoctoral Fellowship from the MSKCC Center for Molecular Imaging and Nanotechnology, and the Alan and Sandra Gerry Metastasis and Tumor Ecosystems Center of MSKCC. Funding Information: The authors acknowledge the Radiochemistry and Molecular Imaging Probe Core, supported by NIH grant P30 CA08748. This study was supported in part by the Geoffrey Beene Cancer Research Center of MSKCC, NIH NCI R35 CA232130, NIH R01 CA244233-01A1. We gratefully acknowledge Mr. William H. and Mrs. Alice Goodwin and the Commonwealth Foundation for Cancer Research and The Center for Experimental Therapeutics of MSKCC. P.M.R. Pereira acknowledges the Tow Foundation Postdoctoral Fellowship from the MSKCC Center for Molecular Imaging and Nanotechnology, and the Alan and Sandra Gerry Metastasis and Tumor Ecosystems Center of MSKCC. Publisher Copyright: {\textcopyright} 2022, World Molecular Imaging Society.",
year = "2022",
month = aug,
doi = "10.1007/s11307-022-01708-2",
language = "English",
volume = "24",
pages = "511--518",
journal = "Molecular Imaging and Biology",
issn = "1536-1632",
number = "4",
}