Feasibility study of indocyanine green for visualizing malignant lesions in colitis-associated colorectal cancer patients with real-time fluorescence endoscopy

Indocyanine green (ICG) has been used in clinical practice for more than 40 years and its safety and preferential accumulation of ICG in tumors has been reported for various tumor types, including colon cancer. However, reports on the clinical assessments of ICG-based molecular endoscopy imaging for pre-cancerous lesions are scarce. Therefore, we determined the percent visualization ability of ICG endoscopy in colitis-associated colon cancer using 30 lesions from an animal model and 16 patient tissues. ICG could detect 100% of carcinoma, 90% adenoma, and 57.1% dysplasia, with little background signal at 30 min after injection via real-time fluorescence endoscopy. Correlation analysis of ICG fluorescence intensity and cancer specific molecules revealed a positive correlation of ICG with c-Met and iNOS (r > 0.5). A high level of iNOS expression increased the cellular nitric oxide in cancer cells than that in normal cells, which was related to the inhibition of drug efflux via ABCB1 transporter down regulation resulted to delayed retention of intracellular ICG. These findings highlight the feasibility of ICG as a detector of pre-cancerous lesions in real-time fluorescence endoscopy and suggest that the mechanism of ICG retention in cancer cells is related with intracellular nitric oxide concentration.