Abstract | BACKGROUND & AIMS:
Inflammatory bowel disease (IBD) is the second most common chronic inflammatory disorder worldwide; however, a noninvasive means of accurately assessing the severity and extent of intestinal inflammation is currently not available. The aim of the present study was to develop a noninvasive imaging modality to detect and evaluate ileitis in SAMP1/YitFc ( SAMP) mice. METHODS: An image-enhancing ultrasound (US) contrast agent, consisting of encapsulated gaseous microbubbles (MB), was developed specifically to bind mucosal addressin cellular adhesion molecule-1 (MAdCAM-1), a mucosal-restricted addressin up-regulated during gut inflammation. MAdCAM-1-targeted MB (MB(M)) were tested for binding specificity on MAdCAM-1 protein and tumor necrosis factor (TNF)-stimulated SVEC4-10 endothelial cells using an in vitro flow chamber assay and for their ability to detect and quantify ileitis by intravital microscopy and transabdominal US. RESULTS: Under in vitro flow conditions, a 100-fold increase in MB(M) binding was observed on MAdCAM-1 protein compared with nonspecific MB (P < .001). TNF-stimulated endothelial cells bound significantly more MB(M) vs nonspecific MB (P < .001), which was abrogated after preincubation with anti-MAdCAM-1 antibodies (P < .001). In vivo, MB(M) specifically accumulated in focal areas of ileal inflammation and produced stronger acoustic echoes, measured by average video intensity, in SAMP vs uninflamed AKR mice (P < .001) or SAMP given nonspecific MB (P < .001). MB(M)-specific video intensity showed a strong positive correlation with total ileal inflammatory scores (R2 = 0.92). CONCLUSIONS: We have developed a novel intravascular US contrast agent targeting MAdCAM-1 that specifically detects and quantifies intestinal inflammation in experimental ileitis, providing the potential for a reliable, noninvasive means to diagnose and monitor disease in patients with IBD.
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Authors | Christopher Bachmann, Alexander L Klibanov, Timothy S Olson, Jason R Sonnenschein, Jesus Rivera-Nieves, Fabio Cominelli, Klaus F Ley, Jonathan R Lindner, Theresa T Pizarro |
Journal | Gastroenterology
(Gastroenterology)
Vol. 130
Issue 1
Pg. 8-16
(Jan 2006)
ISSN: 0016-5085 [Print] United States |
PMID | 16401463
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal
- Cell Adhesion Molecules
- Immunoglobulins
- MADCAM1 protein, human
- Mucoproteins
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Topics |
- Animals
- Antibodies, Monoclonal
- Cell Adhesion Molecules
- Cell Culture Techniques
- Crohn Disease
(diagnostic imaging, physiopathology)
- Flow Cytometry
- Immunoglobulins
(analysis)
- Immunohistochemistry
- Inflammation
- Intestines
(immunology, pathology)
- Mice
- Microbubbles
- Mucoproteins
(analysis)
- Sensitivity and Specificity
- Ultrasonography
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