Detection of colonic dysplasia in vivo using a targeted fluorescent septapeptide and confocal microendoscopy

The merging of targeted probes with new imaging technologies provides a powerful tool for the early detection of cancer. Phage display peptide libraries are highly complex and can be screened for high-affinity ligands with preferential binding to premalignant tissue. An M13 phage library was screened against fresh human colonic adenomas to identify a specific septapeptide sequence, VRPMPLQ, that was synthesized, conjugated with fluorescein, and tested in patients undergoing colonoscopy. Imaging of the topically administered peptide was performed with a novel fluorescence confocal microendoscope delivered through the instrument channel of a standard colonoscope. In vivo imaging at 12 frames-per-second was performed with 50 μm working distance with 2.5 μm (transverse) and 20 μm (axial) resolution. Imaging of the fluorescein-conjugated peptide demonstrated preferential binding to dysplastic colonocytes relative to adjacent normal cells with 81% sensitivity and 78% specificity. The methodology described represents a promising diagnostic imaging approach for the early detection of colon cancer and potentially other epithelial malignancies.