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Mol Cancer Ther. 2012 Oct;11(10):2202-11. doi: 10.1158/1535-7163.MCT-12-0211. Epub 2012 Jul 17.

An optical probe for noninvasive molecular imaging of orthotopic brain tumors overexpressing epidermal growth factor receptor.

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Departments of Radiology, Biomedical Engineering, and Pathology, NFCR Center for Molecular Imaging at Case, Case Western Reserve University, Wearn Building, Room B-42, 11100 Euclid Avenue, Cleveland, OH 44106, USA.


We have developed a near-infrared (NIR) probe that targets cells overexpressing the EGF receptor (EGFR) for imaging glioblastoma brain tumors in live subjects. A peptide specific for the EGFR was modified with various lengths of monodiscrete polyethylene glycol (PEG) units and a NIR Cy5.5 fluorescence dye. The lead compound, compound 2, with one unit of PEG displayed good binding (8.9 μmol/L) and cellular uptake in glioblastoma cells overexpressing EGFR in vitro. The in vivo studies have shown that the probe was able to selectively label glioblastoma-derived orthotopic brain tumors. In vivo image analyses of peptide binding to the tumors using fluorescence-mediated molecular tomography revealed that the compound could distinguish between tumors expressing different levels of EGFR. The data presented here represent the first demonstration of differential quantitation of tumors expressing EGFR in live animals by a targeted NIR fluorescence probe using a molecular imaging device.

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