期刊
出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2008072118
关键词
early detection; fluorescence; endoscopy; activity-based probe; high-risk patients
资金
- NIH [R01 EB028628, R01 EB026285]
- Will-Foundation Berlin
- Canary Center for Early Detection Seed Grant
- Canary Foundation
- Stanford ChEM-H Chemistry/Biology Interface Predoctoral Training Program [DGE-114747]
- NSF Graduate Research Fellowship Grant [DGE-114747]
- Deutsche Krebshilfe Grant [111902]
- German Research Society (Deutsche Forschungsgemeinschaft [DFG]) [Sonderforschungsbereich-824 (SFB-824/3 2017), SFB 1371, SFB 1335]
Fluorescently labeled probes show great potential for clinical application in highlighting gastrointestinal lesions, providing fluorescence-guided surveillance and enhancing histopathological analysis by highlighting areas of dysplasia as small as 400 microns, even in tissues with severe inflammation and ulceration.
Fluorescence imaging is currently being actively developed for surgical guidance; however, it remains underutilized for diagnostic and endoscopic surveillance of incipient colorectal cancer in high-risk 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 mu m, 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据