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Updated: Jan 2, 2026
Nanosensors to Detect Protease Activity In Vivo for Noninvasive Diagnostics
Published on: July 16, 2018
Detection of colonic neoplasia in vivo using near-infrared-labeled peptide targeting cMet
Xiaoli Wu1, Juan Zhou1, Fa Wang1
1Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
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.
Insights
A new fluorescent peptide targets cMet, improving the endoscopic detection of colorectal polyps, including flat and depressed lesions often missed by standard methods. This molecular imaging approach enhances diagnostic accuracy for pre-malignant conditions.
Area of Science:
- Molecular imaging
- Gastroenterology
- Oncology
Background:
- White light colonoscopy frequently misses flat and depressed colorectal lesions.
- Early detection of pre-malignant lesions is crucial for effective colorectal cancer prevention.
Purpose of the Study:
- To develop and evaluate a novel molecular imaging probe for enhanced endoscopic detection of colorectal polyps.
- To assess the specificity and efficacy of a cMet-targeting fluorescent peptide for identifying pre-malignant lesions.
Main Methods:
- Development of a near-infrared (NIR) fluorescently-labeled peptide targeting the cMet receptor.
- In vitro validation using cell staining, knockdown, and competition assays.
- In vivo feasibility study in a mouse model (CPC;Apc) and ex vivo analysis of human colon specimens.
Main Results:
- The cMet-specific peptide probe demonstrated high binding affinity and fast onset for topical administration.
- In vivo imaging in mice showed significantly improved target-to-background ratios for detecting both polypoid and non-polypoid lesions.
- Human colon specimens confirmed greater binding of the probe to adenomas compared to hyperplastic polyps and normal mucosa.
Conclusions:
- A cMet-specific peptide probe shows promise for improving endoscopic detection of pre-malignant colorectal lesions.
- This molecular imaging strategy can enhance diagnostic performance and guide tissue biopsy during colonoscopy.
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