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Bioconjug Chem. 2015 Apr 15;26(4):660-8. doi: 10.1021/bc500597y. Epub 2015 Mar 30.

Optical imaging of targeted β-galactosidase in brain tumors to detect EGFR levels.

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†Department of Radiology and Radiological Sciences, ‡Center of Biomedical Imaging, and §Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, United States.
∥Department of Biomedical Engineering, ⊥Case Center for Imaging Research, and #The NFCR Center for Molecular Imaging, Case Western Reserve University, Cleveland, Ohio 44106, United States.


A current limitation in molecular imaging is that it often requires genetic manipulation of cancer cells for noninvasive imaging. Other methods to detect tumor cells in vivo using exogenously delivered and functionally active reporters, such as β-gal, are required. We report the development of a platform system for linking β-gal to any number of different ligands or antibodies for in vivo targeting to tissue or cells, without the requirement for genetic engineering of the target cells prior to imaging. Our studies demonstrate significant uptake in vitro and in vivo of an EGFR-targeted β-gal complex. We were then able to image orthotopic brain tumor accumulation and localization of the targeted enzyme when a fluorophore was added to the complex, as well as validate the internalization of the intravenously administered β-gal reporter complex ex vivo. After fluorescence imaging localized the β-gal complexes to the brain tumor, we topically applied a bioluminescent β-gal substrate to serial sections of the brain to evaluate the delivery and integrity of the enzyme. Finally, robust bioluminescence of the EGFR-targeted β-gal complex was captured within the tumor during noninvasive in vivo imaging.

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