. We propose to establish an integrated Specialized Research Resource Center comprised of investigators from Stanford University, Vanderbilt University, University of Florida and Optical Biopsy Technologies, Inc (OBTI) to perform collaborative translational research in optical imaging and spectroscopy for the detection of diseases of the epithelium. This network will develop a consensus process and methodology for applying the in vivo use of fluorescence contrast agents applied to molecular targets to be detected by endoscopy and confocal microscopy. The key engineering components of this program include the development of a miniature confocal microscope fabricated with MEMS technology and the adaptation of an existing white light/fluorescence endoscopy system to detect fluorescence contrast agents by the Stanford University Dept of Electrical Engineering and OBTI. The probe chemistries of the program include the design and synthesis of compounds targeted to COX-2 by Vanderbilt University, and the identification and characterization of peptides that bind to cell surface markers associated with neoplastic changes by the Stanford University Dept of Pediatrics. Clinical application of the instrumentation and probes for endoscopy will be evaluated by by the Stanford University Division of Gastroenterology and validated by the Dept. of Pathology at the University of Florida. Confocal microscopy is a powerful imaging technique that performs optical sectioning in biological tissue with sub-cellular resolution. It is capable of simultaneously collecting images of reflectance for characterizing cellular and tissue morphology and of fluorescence for detecting the biochemical and molecular properties of cells and tissue with complete spatial registration. For translation of confocal methodologies to clinical detection and diagnosis we propose the following: 1) develop a novel miniature dual axes confocal microscope using MEMS technology for reflectance imaging at lambda = 1345 nm to evaluate human patients with a history of Barrett's esophagus for the presence of neoplasia, 2) identify molecular markers of neoplasia in the esophagus using a phage display library to screen for small peptides that bind neoplastic mucosa and not non-neoplastic, conjugate these peptides to near-infrared (NIR) dyes, including indocyanine green, Cy 7 and Alexa fluor 750, and evaluate the use of these conjugates for identifying and localizing neoplasia in animal models and human subjects with fluorescence using lamda = 750 nm excitation, and 3) synthesize derivatives of NSAIDS containing functional targeted to COX-2, conjugate these derivatives to the aforementioned NIR dyes, evaluate the use of these conjugates for identifying and localizing neoplasia in animal models and human subjects with fluorescence.
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