S. Liu1, K. Cox1, S. Amirfakhri1, S. Jaiswal1, R. Hoffman1, S. Batra2, M. Primeaux2, P. Dhawan2, S. Talib2, A. Mohs2, M. Bouvet1 1University of California, San Diego, Surgery, San Diego, CA, USA 2University Of Nebraska College Of Medicine, Omaha, NE, USA
Introduction:
Early detection and removal of pre-malignant polyps during colonoscopy remains the best way to prevent colon cancer. Colonoscopy is technically challenging and can have miss rates between 9% – 27% for pre-malignant polyps up to 1 cm in diameter. Additionally, hyperplastic polyps (HP) have little to no malignant potential but can be indistinguishable from pre-malignant sessile serrated adenomas (SSA) on visual exam. This study uses Claudin-1 antibodies conjugated to near-infrared fluorophores to increase detection of precancerous polyps in adenomatous polyposis coli flox mice with a Cdx2-Cre transgene (CPC-APC) that develop colonic polyps with the goal of translation to human use.
Methods:
CPC-APC mice at age 12 weeks at which time colonic polyps have developed were used for this study. Claudin-1 antibody conjugated to IRDye800 (Claudin-1-IR800) was administered intravenously at a dose of 100 ug. Mice were sacrificed post injection at 48 and 72 hour timepoints. Ex-vivo colon imaging was performed using the Pearl and the Stryker 1688 fluorescent imaging systems. Immunohistochemistry of the polyps was performed to confirm Claudin-1 expression. Polyp to background fluroescence signal ratios (PBR) were calculated.
Results:
Four mice were used yielding a total of 15 polyps that were analyzed. The presence of observed polyps on gross examination was confirmed via histology. The PBR at 48 hours post injection was 6.8 ± 3.18 and at 72 hours it was 7.95 ± 0.78 (P = 0.093). Overall, the average PBR was 6.81 ± 2.9, resulting in an over 6-fold fluorescence signal intensity at the site of polyps. Immunohistochemistry confirmed strong expression of Claudin-1 within the polyps. The Stryker 1688 laparoscope was used on the gross colon specimens to confirm visibility of polyps using a commercially available clinical fluorescence imaging system. The fluorescence signal could be definitively detected in polyps as small as 1mm in mice that were invisible in bright light (see Figure).
Conclusion:
Claudin-1-IR800 demonstrated high sensitivity for polyp identification in the CPC-APC mice with an average PBR of >6. Polyps could be detected as small as 1 mm that were invisible in bright light, greatly improving the visual accuracy in polyp identification. Future studies are planned that translate the present findings to clinical practice.