Detection of colonic neoplasia in vivo using near-infrared-labeled peptide targeting cMet.
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ABSTRACT: White light colonoscopy is widely used to detect colorectal polyps, but flat and depressed lesions are often missed. Here, we report a molecular imaging strategy to potentially improve diagnostic performance by developing a fluorescently-labeled peptide specific for cMet. This 7mer is conjugated to Cy5.5, a near-infrared (NIR) cyanine dye. Specific binding to cMet was confirmed by cell staining, knockdown, and competition assays. The probe showed high binding affinity (kd?=?57?nM) and fast onset (k?=?1.6?min) to support topical administration in vivo. A mouse model (CPC;Apc) that develops spontaneous adenomas that overexpress cMet was used to demonstrate feasibility for real time in vivo imaging. This targeting ligand showed significantly higher target-to-background (T/B) ratio for polypoid and non-polypoid lesions by comparison with a scrambled control peptide. Immunofluorescence staining on human colon specimens show significantly greater binding to tubular and sessile serrated adenomas versus hyperplastic polyps and normal mucosa. These results demonstrate a peptide specific for cMet that is promising for endoscopic detection of pre-malignant lesions and guiding of tissue biopsy.
SUBMITTER: Wu X
PROVIDER: S-EPMC6884535 | biostudies-literature | 2019 Nov
REPOSITORIES: biostudies-literature
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