Detection of early adenocarcinoma of the esophagogastric junction by spraying an enzyme-activatable fluorescent probe targeting Dipeptidyl peptidase-IV
Keiko Yamamoto,
Shunsuke Ohnishi,
Takeshi Mizushima,
Junichi Kodaira,
Masayoshi Ono,
Yutaka Hatanaka,
Kanako C. Hatanaka,
Yugo Kuriki,
Mako Kamiya,
Nobuyuki Ehira,
Keisuke Shinada,
Hiroaki Takahashi,
Yuichi Shimizu,
Yasuteru Urano,
Naoya Sakamoto
Affiliations
Keiko Yamamoto
Division of Endoscopy, Hokkaido University Hospital
Shunsuke Ohnishi
Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine
Takeshi Mizushima
Department of Gastroenterology, Japanese Red Cross Kitami Hospital
Junichi Kodaira
Department of Gastroenterology, Keiyukai Daini Hospital
Masayoshi Ono
Department of Gastroenterology, Hakodate Municipal Hospital
Yutaka Hatanaka
Department of Surgical Pathology, Hokkaido University Hospital
Kanako C. Hatanaka
Department of Surgical Pathology, Hokkaido University Hospital
Yugo Kuriki
Laboratory of Chemical Biology and Molecular Imaging, Graduate School of Medicine, University of Tokyo
Mako Kamiya
Laboratory of Chemical Biology and Molecular Imaging, Graduate School of Medicine, University of Tokyo
Nobuyuki Ehira
Department of Gastroenterology, Japanese Red Cross Kitami Hospital
Keisuke Shinada
Department of Gastroenterology, Keiwakai Ebetsu Hospital
Hiroaki Takahashi
Department of Gastroenterology, Keiyukai Daini Hospital
Yuichi Shimizu
Division of Endoscopy, Hokkaido University Hospital
Yasuteru Urano
Laboratory of Chemical Biology and Molecular Imaging, Graduate School of Medicine, University of Tokyo
Naoya Sakamoto
Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine
Abstract Background It is still difficult to detect and diagnose early adenocarcinoma of the esophagogastric junction (EGJ) using conventional endoscopy or image-enhanced endoscopy. A glutamylprolyl hydroxymethyl rhodamine green (EP-HMRG) fluorescent probe that can be enzymatically activated to become fluorescent after the cleavage of a dipeptidyl peptidase (DPP)-IV-specific sequence has been developed and is reported to be useful for the detection of squamous cell carcinoma of the head and neck, and esophagus; however, there is a lack of studies that focuses on detecting EGJ adenocarcinoma by fluorescence molecular imaging. Therefore, we investigated the visualization of early EGJ adenocarcinoma by applying EP-HMRG and using clinical samples resected by endoscopic submucosal dissection (ESD). Methods Fluorescence imaging with EP-HMRG was performed in 21 clinical samples resected by ESD, and the fluorescence intensity of the tumor and non-tumor regions of interest was prospectively measured. Immunohistochemistry was also performed to determine the expression of DPP-IV. Results Fluorescence imaging of the clinical samples showed that the tumor lesions were visualized within a few minutes after the application of EP-HMRG, with a sensitivity, specificity, and accuracy of 85.7, 85.7, and 85.7%, respectively. However, tumors with a background of intestinal metaplasia did not have a sufficient contrast-to-background ratio since complete intestinal metaplasia also expresses DPP-IV. Immunohistochemistry measurements revealed that all fluorescent tumor lesions expressed DPP-IV. Conclusions Fluorescence imaging with EP-HMRG could be useful for the detection of early EGJ adenocarcinoma lesions that do not have a background of intestinal metaplasia.
