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Rapid Cancer Detection by Topically Spraying a γ-Glutamyltranspeptidase–Activated Fluorescent Probe

renchunxiao 添加于 2011/11/25 14:23:07  2650次阅读 | 1次推荐 | 9个评论

The ability of the unaided human eye to detect small cancer foci or accurate borders between cancer and normal tissue duringsurgery or endoscopy is limited. Fluorescent probes are useful for enhancing visualization of small tumors but are typicallylimited by either high background signal or the requirement for administration hours to days before use. We synthesized arapidly activatable, cancer-selective fluorescence imaging probe, γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG), withintramolecular spirocyclic caging for complete quenching. Activation occurs by rapid one-step cleavage of glutamate with γ-glutamyltranspeptidase(GGT), which is not expressed in normal tissue, but is overexpressed on the cell membrane of various cancer cells, thus leadingto complete uncaging and dequenching of the fluorescence probe. In vitro activation of gGlu-HMRG was evident in 11 human ovariancancer cell lines tested. In vivo in mouse models of disseminated human peritoneal ovarian cancer, activation of gGlu-HMRGoccurred within 1 min of topically spraying the tumor, creating high signal contrast between the tumor and the background.The gGlu-HMRG probe is practical for clinical application during surgical or endoscopic procedures because of its rapid andstrong activation upon contact with GGT on the surface of cancer cells.

作 者:Urano, Yasuteru; Sakabe, Masayo; Kosaka, Nobuyuki; Ogawa, Mikako; Mitsunaga, Makoto; Asanuma, Daisuke; Kamiya, Mako; Young, Matthew R.; Nagano, Tetsuo; Choyke, Peter L.; Kobayashi, Hisataka
期刊名称: Science Translational Medicine
期卷页: 11/23/2011 第3卷 第110期 110ra119~110ra119页
学科领域:医学科学 » 肿瘤学 » 肿瘤病因
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原文链接:http://stm.sciencemag.org/content/3/110/110ra119.abstract?sid=f43070a4-8268-44e0-aa94-0593a49d7df9
DOI: 10.1126/scitranslmed.3002823
ISBN: 1946-6234
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