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

Yim JJ, Harmsen S, Flisikowski K, Flisikowska T, Namkoong H, Garland M, Van Den Berg NS, Vilches-Moure JG, Schnieke A, Saur D, Glasl S, Gorpas D, Habtezion A, Ntziachristos V, Contag CH, Gambhir SS, Bogyo M, Rogalla S (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Proceedings of the National Academy of Sciences of the United States of America National Academy of Sciences

Book Volume: 118

Article Number: e2008072118

Journal Issue: 1

DOI: 10.1073/pnas.2008072118

Abstract

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.

Involved external institutions

Technische Universität München (TUM) DE Germany (DE) Stanford University US United States (USA) (US) Stanford Medicine US United States (USA) (US) Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE) Michigan State University US United States (USA) (US)

How to cite

APA:

Yim, J.J., Harmsen, S., Flisikowski, K., Flisikowska, T., Namkoong, H., Garland, M.,... 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). https://doi.org/10.1073/pnas.2008072118

MLA:

Yim, Joshua 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).

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