Abstract
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.
References
1.
Pox CP: Controversies in colorectal cancer screening. Digestion 2014;89:274-281.
[PubMed]
2.
Nishihara R, Wu K, Lochhead P, Morikawa T, Liao X, Qian ZR, Inamura K, Kim SA, Kuchiba A, Yamauchi M, Imamura Y, Willett WC, Rosner BA, Fuchs CS, Giovannucci E, Ogino S, Chan AT: Long-term colorectal-cancer incidence and mortality after lower endoscopy. N Engl J Med 2013;369:1095-1105.
[PubMed]
3.
Shaukat A, Mongin SJ, Geisser MS, Lederle FA, Bond JH, Mandel JS, Church TR: Long-term mortality after screening for colorectal cancer. N Engl J Med 2013;369:1106-1114.
[PubMed]
4.
Brooker JC, Saunders BP, Shah SG, Thapar CJ, Thomas HJ, Atkin WS, et al: Total colonic dye-spray increases the detection of diminutive adenomas during routine colonoscopy: a randomized controlled trial. Gastrointest Endosc 2002;56:333-338.
[PubMed]
5.
Fujii T, Hasegawa RT, Saitoh Y, Fleischer D, Saito Y, Sano Y, Kato S: Chromoscopy during colonoscopy. Endoscopy 2001;33:1036-1041.
[PubMed]
6.
Sano Y, Ikematsu H, Fu KI, Emura F, Katagiri A, Horimatsu T, Kaneko K, Soetikno R, Yoshida S: Meshed capillary vessels by use of narrow-band imaging for differential diagnosis of small colorectal polyps. Gastrointest Endosc 2009;69:278-283.
[PubMed]
7.
Uraoka T, Saito Y, Matsuda T, Sano Y, Ikehara H, Mashimo Y, et al: Detectability of colorectal neoplastic lesions using a narrow-band imaging system: a pilot study. J Gastroenterol Hepatol 2008;23:1810-1815.
[PubMed]
8.
Matsuda T, Saito Y, Fu KI, Uraoka T, Kobayashi N, Nakajima T, Ikehara H, Mashimo Y, Shimoda T, Murakami Y, Parra-Blanco A, Fujimori T, Saito D: Does autofluorescence imaging videoendoscopy system improve the colonoscopic polyp detection rate? A pilot study. Am J Gastroenterol 2008;103:1926-1932.
[PubMed]
9.
Shahid MW, Buchner AM, Heckman MG, Krishna M, Raimondo M, Woodward T, Wallace MB: Diagnostic accuracy of probe-based confocal laser endomicroscopy and narrow band imaging for small colorectal polyps: a feasibility study. Am J Gastroenterol 2012;107:231-239.
[PubMed]
10.
Fujii T, Rembacken BJ, Dixon MF, Yoshida S, Axon AT: Flat adenomas in the United Kingdom: are treatable cancers being missed? Endoscopy 1998;30:437-443.
[PubMed]
11.
Rembacken BJ, Fujii T, Cairns A, Dixon MF, Yoshida S, Chalmers DM, Axon AT: Flat and depressed colonic neoplasms: a prospective study of 1,000 colonoscopies in the UK. Lancet 2000;355:1211-1214.
[PubMed]
12.
Tsuda S, Veress B, Tóth E, Fork FT: Flat and depressed colorectal tumours in a southern Swedish population: a prospective chromoendoscopic and histopathological study. Gut 2002;51:550-555.
[PubMed]
13.
Tamura S, Nakajo K, Yokoyama Y, Ohkawauchi K, Yamada T, Higashidani Y, Miyamoto T, Ueta H, Onishi S: Evaluation of endoscopic mucosal resection for laterally spreading rectal tumors. Endoscopy 2004;36:306-312.
[PubMed]
14.
Uraoka T, Saito Y, Matsuda T, Ikehara H, Gotoda T, Saito D, Fujii T: Endoscopic indications for endoscopic mucosal resection of laterally spreading tumours in the colorectum. Gut 2006;55:1592-1597.
[PubMed]
15.
Saito Y, Fujii T, Kondo H, Mukai H, Yokota T, Kozu T, Saito D: Endoscopic treatment for laterally spreading tumors in the colon. Endoscopy 2001;33:682-686.
[PubMed]
16.
Saito Y, Uraoka T, Yamaguchi Y, Hotta K, Sakamoto N, Ikematsu H, Fukuzawa M, Kobayashi N, Nasu J, Michida T, Yoshida S, Ikehara H, Otake Y, Nakajima T, Matsuda T, Saito D: A prospective, multicenter study of 1,111 colorectal endoscopic submucosal dissections (with video). Gastrointest Endosc 2010;72:1217-1225.
[PubMed]
17.
Frangioni JV: New technologies for human cancer imaging. J Clin Oncol 2008;26:4012-4021.
[PubMed]
18.
Pompella A, de Tata V, Paolicchi A, Zunino F: Expression of γ-glutamyltransferase in cancer cells and its significance in drug resistance. Biochem Pharmacol 2006;71:231-238.
[PubMed]
19.
Hanigan MH, Frierson HF Jr, Brown JE, Lovell MA, Taylor PT: Human ovarian tumors express γ-glutamyl transpeptidase. Cancer Res 1994;54:286-290.
[PubMed]
20.
Yao D, Jiang D, Huang Z, Lu J, Tao Q, Yu Z, Meng X: Abnormal expression of hepatoma specific γ-glutamyl transferase and alteration of γ-glutamyl transferase gene methylation status in patients with hepatocellular carcinoma. Cancer 2000;88:761-769.
[PubMed]
21.
Schäfer C, Fels C, Brucke M, Holzhausen HJ, Bahn H, Wellman M, Visvikis A, Fischer P, Rainov NG: γ-Glutamyl transferase expression in higher-grade astrocytic glioma. Acta Oncol 2001;40:529-535.
[PubMed]
22.
Urano Y, Sakabe M, Kosaka N, Ogawa M, Mitsunaga M, Asanuma D, Kamiya M, Young MR, Nagano T, Choyke PL, Kobayashi H: Rapid cancer detection by topically spraying a γ-glutamyltranspeptidase-activated fluorescent probe. Sci Transl Med 2011;3:110ra119.
[PubMed]
23.
Mitsunaga M, Kosaka N, Choyke PL, Young MR, Dextras CR, Saud SM, Colburn NH, Sakabe M, Nagano T, Asanuma D, Urano Y, Kobayashi H: Fluorescence endoscopic detection of murine colitis-associated colon cancer by topically applied enzymatically rapid-activatable probe. Gut 2013;62:1179-1186.
[PubMed]
24.
Urano Y, Asanuma D, Hama Y, Koyama Y, Barrett T, Kamiya M, Nagano T, Watanabe T, Hasegawa A, Choyke PL, Kobayashi H: Selective molecular imaging of viable cancer cells with pH-activatable fluorescence probes. Nat Med 2009;15:104-109.
[PubMed]
25.
Munjal DD: Concurrent measurements of carcinoembryonic antigen, glucosephosphate isomerase, γ-glutamyltransferase, and lactate dehydrogenase in malignant, normal adult, and fetal colon tissues. Clin Chem 1980;26:1809-1812.
[PubMed]
26.
Kudo S, Kashida H, Nakajima T, Tamura S, Nakajo K: Endoscopic diagnosis and treatment of early colorectal cancer. World J Surg 1997;21:694-701.
[PubMed]
27.
Kudo S, Kashida H, Tamura T, Kogure E, Imai Y, Yamano H, Hart AR: Colonoscopic diagnosis and management of nonpolypoid early colorectal cancer. World J Surg 2000;24:1081-1090.
[PubMed]
28.
Japanese Society for Cancer of the Colon and Rectum: Japanese Classification of Colorectal Carcinoma, ed 8. Tokyo, Kanehara Shuppan, 2013.
29.
Urano Y: In vivo cancer detection with a newly designed fluorescent probe (in Japanese). Gan To Kagaku Ryoho 2013;40:299-303.
[PubMed]
30.
Kobayashi H, Ogawa M, Alford R, Choyke PL, Urano Y: New strategies for fluorescent probe design in medical diagnostic imaging. Chem Rev 2010;110:2620-2640.
[PubMed]
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