A Pilot Study of Fluorescent Imaging of Colorectal Tumors Using a γ-Glutamyl-Transpeptidase-Activatable Fluorescent ProbeSato C.a, e · Abe S.a · Saito Y.a · So Tsuruki E.a · Takamaru H.a · Makazu M.a, e · Sato Y.a · Sasaki H.a · Tanaka H.a · Ikezawa N.a · Yamada M.a · Sakamoto T.a · Nakajima T.a · Matsuda T.a · Kushima R.b · Kamiya M.c · Maeda S.f · Urano Y.c, d
aEndoscopy Division and bPathology Division, National Cancer Center Hospital, cLaboratory of Chemical Biology and Molecular Imaging, Graduate School of Medicine, The University of Tokyo, and dBasic Research Program, Japan Science and Technology Agency (JST), Tokyo, eGastroenterological Center, Yokohama City University Medical Center, and fDepartment of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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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.
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