Early detection of structural or molecular changes in dysplastic epithelial tissues is crucial for cancer screening and surveillance. Multi-targeting molecular endoscopic fluorescence imaging may improve noninvasive detection of precancerous lesions in the colon. Here, we report the first clinically compatible, wide-field-of-view, multi-color fluorescence endoscopy with a leached fiber bundle scope using a porcine model. A porcine colon model that resembles the human colon is used for the detection of surrogate tumors composed of multiple biocompatible fluorophores (FITC, ICG, and heavy metal-free quantum dots (hfQDs)). With an ex vivo porcine colon tumor model, molecular imaging with hfQDs conjugated with MMP14 antibody was achieved by spraying molecular probes on a mucosa layer that contains xenograft tumors. With an in vivo porcine colon embedded with surrogate tumors, target-to-background ratios of 3.36 ± 0.43, 2.70 ± 0.72, and 2.10 ± 0.13 were achieved for FITC, ICG, and hfQD probes, respectively. This promising endoscopic technology with molecular contrast shows the capacity to reveal hidden tumors and guide treatment strategy decisions. Sharma, "Comparison of the yield and miss rate of narrow band imaging and white light endoscopy in patients undergoing screening or surveillance colonoscopy: a meta-analysis," Am. J. Gastroenterol. 107(3), 363-371 (2012). 2. Sturm, M.B. and T.D. Wang," Emerging optical methods for surveillance of Barrett's oesophagus, " Gut, gutjnl-2013" Gut, gutjnl- -306706 (2015. Rat, P. Roignot, J. Faivre, P. Laurent-Puig, and F. Piard, "Mutations in the RAS-MAPK, PI (3) K (phosphatidylinositol-3-OH kinase) signaling network correlate with poor survival in a population-based series of colon cancers," Int.
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