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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.*

A protease-activated, near-infrared fluorescent probe for early endoscopic detection of premalignant gastrointestinal lesions.

Proc. Natl. Acad. Sci. U.S.A. 118:e2008072118 (2021)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Activity-based Probe ; Early Detection ; Endoscopy ; Fluorescence ; High-risk Patients; Depressed Colorectal Neoplasms; Endothelial Growth-factor; Nonpolypoid Flat; Cancer; Surveillance; Predisposes; Colonoscopy; Mutation; Polyps; Model
ISSN (print) / ISBN 0027-8424
e-ISSN 1091-6490
Quellenangaben Volume: 118, Issue: 1, Pages: , Article Number: e2008072118 Supplement: ,
Publisher National Academy of Sciences
Publishing Place 2101 Constitution Ave Nw, Washington, Dc 20418 Usa
Reviewing status Peer reviewed
Grants NIBIB NIH HHS