Imaging Matrix Metalloproteases in Spontaneous Colon Tumors: Validation by Correlation with Histopathology

Abstract

The use of fluorescent probes in conjunction with white-light colonoscopy is a promising strategy for improving the detection of precancerous colorectal lesions, in particular flat (sessile) lesions that do not protrude into the lumen of the colon. We describe a method for determining the sensitivity and specificity of an enzymatically activated near-infrared probe (MMPSense680) for the detection of colon lesions in a mouse model (APC^+/Min-FCCC) of spontaneous colorectal cancer. Fluorescence intensity correlates directly with the activity of matrix metalloproteinases (MMPs). Overexpression of MMPs is an early event in the development of colorectal lesions. Although the probe employed serves as a reporter of the activity of MMPs, our method can be applied to any fluorescent probe that targets an early molecular event in the development of colorectal tumors.

Keywords: Activated imaging probes; Colonoscopy; Colorectal cancer; Early cancer detection; Fluorescence imaging; Imaging; Matrix metalloproteinases; Mice; Min mice; Near-infrared imaging.