Abstract
BACKGROUND
Early detection and removal of polyps for primary colon cancer prevention during colonoscopy are still fraught with significant miss rates. In the current study, we determined the ability of claudin-1 (CLDN1) antibodies conjugated to near-infrared fluorophores to target and visualize colonic polyps with high resolution in the CPC-APC mouse colonic polyp model.
METHODS
CPC-APC mice that developed distal colon polyps at 12 weeks of age were used in the present study. The formation of polyps was confirmed by mouse colonoscopy using the ColoView system (Karl Stortz). For polyp labeling, anti-CLDN1 and control immunoglobulin G (IgG) antibodies were conjugated to IRDye800 and 50, 100, and 150 μg doses were administered intravenouly to CPC-APC mice. Mice were sacrificed at different time points, and colons were harvested for imaging using the LI-COR Pearl Small Animal Imaging System. Polyp-to-background fluorescence intensity ratios (PBRs) were calculated for each polyp. Histology and immunohistochemistry (IHC) were performed on the polyps.
RESULTS
A total of 9 mice were used in the experiment, with a total of 45 polyps analyzed. The presence of observed polyps on gross examination was confirmed via histology. CLDN1-IRDye800 had a PBR of 7.6 ± 3.9, which was significantly higher than the nonspecific IgG-IRDye800 control (P =.0428). CLDN1-IRDye800 was further analyzed and overall had a similar range of PBR with 50, 100, and 150 μg injections at 72 h and had a statistically significant higher PBR of 8.9 ± 4.2 than the IgG-IRDye800 control (P =.0184) at 150 μg. Adenomatous polyps as small as 1 mm could be identified using CLDN1-IRDye800. Hematoxylin and eosin staining confirmed adenomatous polyps with high-grade dysplasia, and IHC confirmed the expression of CLDN1.
CONCLUSION
CLDN1-IRDye800 enabled polyp visualization with ultrahigh-resolution fluorescence imaging technology in CPC-APC mice. Polyps as small as 1 mm could be visualized, indicating clinical potential to overcome the current limitations of colonic polyp detection.