BACKGROUND: Suitable diagnostics could identify patients who might benefit from targeted therapies. Molecular imaging is a promising method estimating the expression of specific molecules in vivo, and the goal of this study was to evaluate a radioiodinated anti-epidermal growth factor receptor (EGFR) human Fab as a molecular imaging agent for diagnosis. MATERIALS AND METHODS: Three human tumor cell lines representing tumors with different levels of EGFR expression were selected and their corresponding xenografts produced. (125)I was conjugated to a human anti-EGFR Fab that recognizes the native extracellular domain of EGFR evidenced by immunoprecipitation (IP) and fluorescence-activated cell sorting (FACS) assays. Single-photon-emission computed tomography (SPECT) imaging of (125)I-Fab being administered to nude mice bearing xenografts were obtained, and further analyzed by region of interest (ROI) assay. RESULTS: The (125)I-Fab was achieved successfully without losing its immunoreactivity. The scintigrams as well as ROI assay showed that (125)I-Fab was able to clearly quantitatively distinguish the different expression levels of EGFR in vivo. CONCLUSION: (125)I-Fab is a potential molecular imaging agent for clinical diagnosis of EGFR-overexpressing tumors.
BACKGROUND: Suitable diagnostics could identify patients who might benefit from targeted therapies. Molecular imaging is a promising method estimating the expression of specific molecules in vivo, and the goal of this study was to evaluate a radioiodinated anti-epidermal growth factor receptor (EGFR) humanFab as a molecular imaging agent for diagnosis. MATERIALS AND METHODS: Three humantumor cell lines representing tumors with different levels of EGFR expression were selected and their corresponding xenografts produced. (125)I was conjugated to a human anti-EGFRFab that recognizes the native extracellular domain of EGFR evidenced by immunoprecipitation (IP) and fluorescence-activated cell sorting (FACS) assays. Single-photon-emission computed tomography (SPECT) imaging of (125)I-Fab being administered to nude mice bearing xenografts were obtained, and further analyzed by region of interest (ROI) assay. RESULTS: The (125)I-Fab was achieved successfully without losing its immunoreactivity. The scintigrams as well as ROI assay showed that (125)I-Fab was able to clearly quantitatively distinguish the different expression levels of EGFR in vivo. CONCLUSION: (125)I-Fab is a potential molecular imaging agent for clinical diagnosis of EGFR-overexpressing tumors.
Authors: Marleen van Oosten; Lucia Ma Crane; Joost Bart; Fijs W van Leeuwen; Gooitzen M van Dam Journal: Transl Oncol Date: 2011-04-01 Impact factor: 4.243
Authors: Datta E Ponde; ZiFen Su; Alan Berezov; Hongtao Zhang; Abbas Alavi; Mark I Greene; Ramachandran Murali Journal: Bioorg Med Chem Lett Date: 2011-02-15 Impact factor: 2.823