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Real-Time Vital Optical Imaging of Precancer Using Anti-Epidermal Growth Factor Receptor Antibodies Conjugated to Gold Nanoparticles¹

Departments of Imaging Physics [K. S.], Pathology [A. M.], and Thoracic Head & Neck, Medical Oncology [R. L.] and Center for Biomedical Engineering [M. F.], University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, and Department of Biomedical Engineering, University of Texas, Austin, Texas 78712 [J. A., I. P., R. R-K.]

Recent developments in photonic technology provide the ability to noninvasively image cells in vivo; these new cellular imaging technologies have the potential to dramatically improve the prevention, detection, and therapy of epithelial cancers. Endoscope-compatible microscopies, such as optical coherence tomography and reflectance confocal microscopy, image reflected light, providing a three-dimensional picture of tissue microanatomy with excellent spatial resolution (1–10 µm). However, their ability to image molecular biomarkers associated with cancer is limited. Here, we describe a new class of molecular specific contrast agents for vital reflectance imaging based on gold nanoparticles attached to probe molecules with high affinity for specific cellular biomarkers. The application of gold bioconjugates for vital imaging of precancers is demonstrated using cancer cell suspensions, three-dimensional cell cultures, and normal and neoplastic fresh cervical biopsies. We show that gold conjugates can be delivered topically for imaging throughout the whole epithelium. These contrast agents have potential to extend the ability of vital reflectance microscopies for in vivo molecular imaging. They can potentially enable combined screening, detection, and therapy of disease using inexpensive imaging systems; such tools could allow mass screening of diseases such as cancer in resource-poor settings.

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