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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)
Verlagsversion DOI PMC
Free by publisher
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter 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
Zeitschrift Proceedings of the National Academy of Sciences of the United States of America
Quellenangaben Band: 118, Heft: 1, Seiten: , Artikelnummer: e2008072118 Supplement: ,
Verlag National Academy of Sciences
Verlagsort 2101 Constitution Ave Nw, Washington, Dc 20418 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Biological and Medical Imaging (IBMI)
Förderungen NIBIB NIH HHS