TY - JOUR
T1 - Detection of dysplastic intestinal adenomas using enzyme-sensing molecular beacons in mice
AU - Marten, Katharina
AU - Bremer, Christoph
AU - Khazaie, Khashayarsha
AU - Sameni, Mansoureh
AU - Sloane, Bonnie
AU - Tung, Ching Hsuan
AU - Weissleder, Ralph
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
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U2 - 10.1053/gast.2002.30990
DO - 10.1053/gast.2002.30990
M3 - Article
C2 - 11832455
AN - SCOPUS:0036161155
SN - 0016-5085
VL - 122
SP - 406
EP - 414
JO - Gastroenterology
JF - Gastroenterology
IS - 2
ER -