气候变化领域集成服务门户(CCPortal): A protease-activated, near-infrared fluorescent probe for early endoscopic detection of premalignant gastrointestinal lesions

CCPortal

DOI	10.1073/pnas.2008072118
	A protease-activated, near-infrared fluorescent probe for early endoscopic detection of premalignant gastrointestinal lesions
	Yim J.J.; Harmsen S.; Flisikowski K.; Flisikowska T.; Namkoong H.; Garland M.; Van Den Berg N.S.; Vilches-Moure J.G.; Schnieke A.; Saur D.; Glasl S.; Gorpas D.; Habtezion A.; Ntziachristos V.; Contag C.H.; Gambhir S.S.; Bogyo M.; Rogalla S.
发表日期	2021
ISSN	00278424
卷号	118 期号:1
英文摘要	Fluorescence imaging is currently being actively developed for surgical guidance; however, it remains underutilized for diagnostic and endoscopic surveillance of incipient colorectal cancer in highrisk patients. Here we demonstrate the utility and potential for clinical translation of a fluorescently labeled cathepsin-activated chemical probe to highlight gastrointestinal lesions. This probe stays optically dark until it is activated by proteases produced by tumor-associated macrophages and accumulates within the lesions, enabling their detection using an endoscope outfitted with a fluorescence detector. We evaluated the probe in multiple murine models and a human-scale porcine model of gastrointestinal carcinogenesis. The probe provides fluorescence-guided surveillance of gastrointestinal lesions and augments histopathological analysis by highlighting areas of dysplasia as small as 400 μm, which were visibly discernible with significant tumor-to-background ratios, even in tissues with a background of severe inflammation and ulceration. Given these results, we anticipate that this probe will enable sensitive fluorescence-guided biopsies, even in the presence of highly inflamed colorectal tissue, which will improve early diagnosis to prevent gastrointestinal cancers. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Activity-based probe; Early detection; Endoscopy; Fluorescence; High-risk patients
语种	英语
scopus关键词	fluorescent dye; proteinase; animal experiment; animal model; animal tissue; Article; carcinogenesis; colonoscopy; controlled study; digestive system injury; early cancer diagnosis; endoscopy; enzyme activation; female; gastrointestinal polyposis; high risk patient; histopathology; mouse; near infrared spectroscopy; nonhuman; priority journal; white light endoscopy
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/181153
作者单位	Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305, United States; Department of Radiology, Bio-X Program and Molecular Imaging Program, Stanford University School of Medicine, Stanford, CA 94305, United States; Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Chair of Livestock Biotechnology, Technische Universitat Munchen, Freising, 85354, Germany; Department of Medicine, Division of Gastroenterology & Hepatology, Stanford University School of Medicine, Stanford, CA 94305, United States; Department of Cancer Biology, Stanford University School of Medicine, Stanford, CA 94305, United States; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, United States; Department of Comparative Medicine, Stanford School of Medicine, Stanford, CA 94305, United States; Division of Translational Cancer Research, German Cancer Resea...
推荐引用方式 GB/T 7714	Yim J.J.,Harmsen S.,Flisikowski K.,et al. A protease-activated, near-infrared fluorescent probe for early endoscopic detection of premalignant gastrointestinal lesions[J],2021,118(1).
APA	Yim J.J..,Harmsen S..,Flisikowski K..,Flisikowska T..,Namkoong H..,...&Rogalla S..(2021).A protease-activated, near-infrared fluorescent probe for early endoscopic detection of premalignant gastrointestinal lesions.Proceedings of the National Academy of Sciences of the United States of America,118(1).
MLA	Yim J.J.,et al."A protease-activated, near-infrared fluorescent probe for early endoscopic detection of premalignant gastrointestinal lesions".Proceedings of the National Academy of Sciences of the United States of America 118.1(2021).