Detection of colonic neoplasia in vivo using near-infrared-labeled peptide targeting cMet

Sci Rep. 2019 Nov 29;9(1):17917. doi: 10.1038/s41598-019-54385-7.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenoma / diagnostic imaging*
  • Adenoma / pathology
  • Animals
  • Carbocyanines / chemistry
  • Cell Line, Tumor
  • Colonic Neoplasms / diagnostic imaging*
  • Colonic Neoplasms / pathology
  • Colonoscopy / methods*
  • Colonoscopy / standards
  • Fluorescent Dyes
  • HT29 Cells
  • Humans
  • Image-Guided Biopsy / methods
  • Image-Guided Biopsy / standards
  • Infrared Rays
  • Intestinal Mucosa / metabolism
  • Ligands
  • Mice
  • NIH 3T3 Cells
  • Peptides / chemistry
  • Peptides / pharmacokinetics*
  • Protein Binding
  • Proto-Oncogene Proteins c-met / metabolism*
  • Sensitivity and Specificity

Substances

  • CY5.5 cyanine dye
  • Carbocyanines
  • Fluorescent Dyes
  • Ligands
  • Peptides
  • Proto-Oncogene Proteins c-met