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

BMC Cancer

Research Article

Mitsuteru Natsuizaka¹  Naoya Sakamoto¹  Yuichi Shimizu¹  Shunsuke Ohnishi¹  Yoshimasa Kubota¹  Takeshi Mizushima¹  Hidetaka Hosono¹  Akihiro Homma²  Yutaka Hatanaka³  Kanako C. Hatanaka³  Shouko Ono⁴  Mototsugu Kato⁴  Mako Kamiya⁵  Yasuteru Urano⁶ 

[1] Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, N15, W7, Kita-ku, 060-8638, Sapporo, Japan;Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, N15, W7, Kita-ku, 060-8638, Sapporo, Japan;Department of Surgical Pathology, Hokkaido University Hospital, N14, W5, Kita-ku, 060-8648, Sapporo, Japan;Division of Endoscopy, Hokkaido University Hospital, N14, W5, Kita-ku, 060-8648, Sapporo, Japan;Laboratory of Chemical Biology and Molecular Imaging, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan;Laboratory of Chemical Biology and Molecular Imaging, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan;Japan Agency for Medical Research and Development (AMED)-CREST, 7-1 Ootemachi-1, Chiyoda-ku, 100-0004, Tokyo, Japan;

关键词: Fluorescent imaging;    γ-Glutamyltranspeptidase;    Head and neck squamous cell carcinoma;   

DOI  :  10.1186/s12885-016-2421-z

 received in 2015-12-13, accepted in 2016-06-16,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundDetecting 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.MethodsgGlu-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.ResultsAll 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.ConclusionsFluorescence imaging with gGlu-HMRG would be useful for early detection of HNSCC.

【 授权许可】

CC BY   
© The Author(s). 2016