carbocyanines and Intestinal-Neoplasms

Early detection of colonic polyps can prevent up to 90% of colorectal cancer deaths. Conventional colonoscopy readily detects the majority of premalignant lesions, which exhibit raised morphology. However, lesions that are flat and depressed are often undetected using this method. Therefore, there is a need for molecular-based contrast agents to improve detection rates over conventional colonoscopy. We evaluated a quenched fluorescent activity-based probe (qABP; BMV109) that targets multiple cysteine cathepsins that are overexpressed in intestinal dysplasia in a genetic model of spontaneous intestinal polyp formation and in a chemically induced model of colorectal carcinoma. We found that the qABP selectively targets cysteine cathepsins, resulting in high sensitivity and specificity for intestinal tumors in mice and humans. Additionally, the qABP can be administered by either intravenous injection or by local delivery to the colon, making it a highly valuable tool for improved detection of colorectal lesions using fluorescence-guided colonoscopy.

Topics: Adenomatous Polyposis Coli Protein; Animals; Carbocyanines; Catalytic Domain; Cathepsins; Colonoscopy; Disease Models, Animal; Fluorescent Dyes; Humans; Immunohistochemistry; Intestinal Neoplasms; Male; Mice; Mice, Inbred C57BL; Polyps; Sensitivity and Specificity

We describe the design and construction of a miniaturized multichannel near infrared (NIR) endoscopic imaging system developed for high-resolution imaging of mice. The device allows for simultaneous real-time video images in white light and two independent NIR channels. Testing demonstrated independent acquisition of nanomolar concentrations of fluorochromes Cy5.5 and Cy7. Cross-talk between the NIR channels, partially a result of broad tails in the spectra of commonly used organic fluorochromes, was assessed, modeled for the linear range of the concentration/signal intensity function, and compensated. The calculated compensation was 5.5% and 22% of the total signal intensity in the two channels NIR700 and NIR780, respectively, at equal concentrations of the two fluorochromes. Using a mouse model of colonic adenomatosis, we show that both perfusion and protease activity can be detected simultaneously, independently, and repeatedly in live mice. The developed device should be useful for in vivo imaging of diverse molecular targets.

Topics: Adenoma; Animals; Carbocyanines; Colonic Polyps; Colonoscopy; Disease Models, Animal; Endoscopes; Endoscopy; Image Processing, Computer-Assisted; Intestinal Neoplasms; Mice; Mice, Mutant Strains; Sensitivity and Specificity; Software; Spectroscopy, Near-Infrared