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Fluorescent imaging of superficial head and neck squamous cell carcinoma using a γ-glutamyltranspeptidase-activated targeting agent : a pilot study

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Title: Fluorescent imaging of superficial head and neck squamous cell carcinoma using a γ-glutamyltranspeptidase-activated targeting agent : a pilot study
Authors: Mizushima, Takeshi Browse this author
Ohnishi, Shunsuke Browse this author →KAKEN DB
Shimizu, Yuichi Browse this author →KAKEN DB
Hatanaka, Yutaka Browse this author →KAKEN DB
Hatanaka, Kanako C. Browse this author
Hosono, Hidetaka Browse this author
Kubota, Yoshimasa Browse this author
Natsuizaka, Mitsuteru Browse this author
Kamiya, Mako Browse this author →KAKEN DB
Ono, Shouko Browse this author
Homma, Akihiro Browse this author →KAKEN DB
Kato, Mototsugu Browse this author →KAKEN DB
Sakamoto, Naoya Browse this author →KAKEN DB
Urano, Yasuteru Browse this author
Keywords: Fluorescent imaging
γ-Glutamyltranspeptidase
Head and neck squamous cell carcinoma
Issue Date: 7-Jul-2016
Publisher: BioMed Central
Journal Title: BMC Cancer
Volume: 16
Start Page: 411
Publisher DOI: 10.1186/s12885-016-2421-z
Abstract: Background: Detecting superficial head and neck squamous cell carcinoma (HNSCC) by endoscopy is challenging because of limited morphological hallmarks, and iodine cannot be applied to head and neck lesions due to severe mucosal irritation. γ-glutamyltranspeptidase (GGT), a cell surface enzyme, is overexpressed in several cancers, and it has been reported that γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG), a fluorescent targeting agent which can be enzymatically activated and becomes fluorescent after cleavage of a GGT-specific sequence, can be activated within a few minutes after application to animal models. We investigated whether early HNSCC can be detected by applying gGlu-HMRG to clinical samples. Methods: gGlu-HMRG was applied to four HNSCC cell lines, and fluorescence was observed by fluorescence microscopy and flow cytometry. Immunohistological examination was performed in three recent cases of endoscopic submucosal dissection (ESD) to investigate GGT expression. Fluorescence imaging with gGlu-HMRG in eight clinical samples resected by ESD or surgery was performed, and fluorescence intensity of tumor and normal mucosa regions of interest (ROI) was prospectively measured. Results: All four gGlu-HMRG-applied cell lines emitted green fluorescence. Immunohistological examination demonstrated that GGT was highly expressed in HNSCC of the recent three ESD cases but barely in the normal mucosa. Fluorescence imaging showed that iodine-voiding lesions became fluorescent within a few minutes after application of gGlu-HMRG in all eight resected tumors. Tumor ROI fluorescence intensity was significantly higher than in the normal mucosa five minutes after gGlu-HMRG application. Conclusions: Fluorescence imaging with gGlu-HMRG would be useful for early detection of HNSCC.
Rights: https://creativecommons.org/licenses/by/4.0/
Type: article
URI: http://hdl.handle.net/2115/62385
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 大西 俊介

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