Overexpressed Claudin-1 Can Be Visualized Endoscopically in Colonic Adenomas In Vivo

Area of Science:

• Gastroenterology
• Molecular Imaging
• Oncology

Background:

• Colorectal cancer (CRC) screening relies on detecting precancerous lesions.
• Missed polyps, both polypoid and flat, contribute to CRC incidence and mortality.
• Claudin-1 is identified as a promising molecular target for early CRC detection.

Purpose of the Study:

• To establish proof-of-concept for real-time endoscopic imaging of colonic adenomas.
• To utilize a near-infrared peptide specific for claudin-1 for imaging.
• To investigate claudin-1 as a target for improved CRC detection.

Main Methods:

• Phage display identified the peptide RTSPSSR targeting claudin-1 (amino acids 53-80).
• The peptide was labeled with Cy5.5 and its binding parameters characterized.
• In vivo near-infrared fluorescence imaging was performed endoscopically in a mouse model.
• Immunofluorescence validated peptide binding to human colonic adenomas.

Main Results:

• Claudin-1 gene expression was 2.5-fold higher in human colonic adenomas versus normal tissue.
• The peptide RTSPSSR demonstrated specific binding to claudin-1 with high affinity (42 nmol/L).
• In vivo imaging revealed significantly higher target-to-background ratios for both polypoid and flat adenomas in mice.
• Human adenomas showed significantly greater peptide binding intensity compared to normal and hyperplastic polyps.

Conclusions:

• Claudin-1 is overexpressed in premalignant colonic lesions.
• Endoscopic in vivo detection of colonic adenomas using a near-infrared labeled peptide is feasible.
• This peptide-based imaging approach holds potential for enhanced colorectal cancer screening.