A pilot study of fluorescent imaging of colorectal tumors using a γ-glutamyl-transpeptidase-activatable fluorescent probe.

ABSTRACT

UNLABELLED Backgrounds/Aim: Colorectal laterally spreading tumors (LSTs) are sometimes difficult to visualize even with image-enhanced endoscopy. γ-Glutamyl-transpeptidase (GGT) is a cell surface-associated enzyme that is overexpressed in various types of human cancers. Furthermore, GGT expression is higher in colorectal cancer cells than in normal colorectal mucosa. γ-Glutamyl hydroxymethyl rhodamine green (gGlu-HMRG), an activatable fluorescent probe, is nonfluorescent under a neutral pH and normal cellular environment; however, it turns highly fluorescent upon reaction with GGT. We evaluated ex vivo fluorescent imaging of colorectal LSTs using this GGT-activatable fluorescent probe. METHODS: Between March 2013 and March 2014, 30 endoscopically resected colorectal LSTs were prospectively included in this study. Each was analyzed by first taking a baseline image before spraying, then spraying with gGlu-HMRG onto the freshly resected specimen, and finally taking fluorescent images 15 min after spraying with a dedicated imaging machine. RESULTS: Of the LSTs, 67% rapidly showed positive fluorescent activity. These activities were shown in adenoma (54%) and carcinoma in adenoma (76%), and in LST-granular type (80%) and LST-nongranular type (40%). CONCLUSION: Topically spraying gGlu-HMRG enabled rapid and selective fluorescent imaging of colorectal tumors owing to the upregulated GGT activity in cancer cells.