Detection of dysplastic intestinal adenomas using enzyme-sensing molecular beacons in mice

Katharina Marten, Christoph Bremer, Khashayarsha Khazaie, Mansoureh Sameni, Bonnie Sloane, Ching Hsuan Tung, Ralph Weissleder

Research output: Contribution to journalArticle

186 Scopus citations

Abstract

Background & Aims: Proteases play key roles in the pathogenesis of tumor growth and invasion. This study assesses the expression of cathepsin B in dysplastic adenomatous polyps. Methods: Aged ApcMin/+ mice served as an experimental model for familial adenomatous polyposis. The 4 experimental groups consisted of (a) animals injected with a novel activatable, cathepsin B sensing near infrared fluorescence (NIRF) imaging probe; (b) animals injected with a nonspecific NIRF; (c) uninjected control animals; and (d) non-APCMin/+ mice injected with the cathepsin B probe. Lesions were analyzed by immunohistochemistry, Western blotting, reverse transcription-polymerase chain reaction, and optical imaging. Results: Cathepsin B was consistently overexpressed in adenomatous polyps. When mice were injected intravenously with the cathepsin reporter probe, intestinal adenomas became highly fluorescent indicative of high cathepsin B enzyme activity. Even microscopic adenomas were readily detectable by fluorescence, but not light, imaging. The smallest lesion detectable measured 50 μm in diameter. Adenomas in the indocyanine green and/or noninjected group were only barely detectable above the background. Conclusions: The current experimental study shows that cathepsin B is up-regulated in a mouse model of adenomatous polyposis. Cathepsin B activity can be used as a biomarker to readily identify such lesions, particularly when contrasted against normal adjacent mucosa. This detection technology can be adapted to endoscopy or tomographic optical imaging methods for screening of suspicious lesions and potentially for molecular profiling in vivo.

Original languageEnglish (US)
Pages (from-to)406-414
Number of pages9
JournalGastroenterology
Volume122
Issue number2
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    Marten, K., Bremer, C., Khazaie, K., Sameni, M., Sloane, B., Tung, C. H., & Weissleder, R. (2002). Detection of dysplastic intestinal adenomas using enzyme-sensing molecular beacons in mice. Gastroenterology, 122(2), 406-414. https://doi.org/10.1053/gast.2002.30990