Targeting mucosal addressin cellular adhesion molecule (MAdCAM)-1 to noninvasively image experimental Crohn's disease

Christopher Bachmann, Alexander L. Klibanov, Timothy S. Olson, Jason R. Sonnenschein, Jesus Rivera-Nieves, Fabio Cominelli, Klaus F. Ley, Jonathan Lindner, Theresa T. Pizarro

Research output: Contribution to journalArticle

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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 (MBM) 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 MBM binding was observed on MAdCAM-1 protein compared with nonspecific MB (P <.001). TNF-stimulated endothelial cells bound significantly more MBM vs nonspecific MB (P <.001), which was abrogated after preincubation with anti-MAdCAM-1 antibodies (P <.001). In vivo, MBM 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). MBM-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.

Original languageEnglish (US)
Pages (from-to)8-16
Number of pages9
JournalGastroenterology
Volume130
Issue number1
DOIs
StatePublished - Jan 2006
Externally publishedYes

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Microbubbles
Crohn Disease
Ileitis
Inflammation
Inflammatory Bowel Diseases
Contrast Media
Endothelial Cells
Tumor Necrosis Factor-alpha
Inbred AKR Mouse
Acoustics
Proteins
Antibodies

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Bachmann, C., Klibanov, A. L., Olson, T. S., Sonnenschein, J. R., Rivera-Nieves, J., Cominelli, F., ... Pizarro, T. T. (2006). Targeting mucosal addressin cellular adhesion molecule (MAdCAM)-1 to noninvasively image experimental Crohn's disease. Gastroenterology, 130(1), 8-16. https://doi.org/10.1053/j.gastro.2005.11.009

Targeting mucosal addressin cellular adhesion molecule (MAdCAM)-1 to noninvasively image experimental Crohn's disease. / Bachmann, Christopher; Klibanov, Alexander L.; Olson, Timothy S.; Sonnenschein, Jason R.; Rivera-Nieves, Jesus; Cominelli, Fabio; Ley, Klaus F.; Lindner, Jonathan; Pizarro, Theresa T.

In: Gastroenterology, Vol. 130, No. 1, 01.2006, p. 8-16.

Research output: Contribution to journalArticle

Bachmann, C, Klibanov, AL, Olson, TS, Sonnenschein, JR, Rivera-Nieves, J, Cominelli, F, Ley, KF, Lindner, J & Pizarro, TT 2006, 'Targeting mucosal addressin cellular adhesion molecule (MAdCAM)-1 to noninvasively image experimental Crohn's disease', Gastroenterology, vol. 130, no. 1, pp. 8-16. https://doi.org/10.1053/j.gastro.2005.11.009
Bachmann, Christopher ; Klibanov, Alexander L. ; Olson, Timothy S. ; Sonnenschein, Jason R. ; Rivera-Nieves, Jesus ; Cominelli, Fabio ; Ley, Klaus F. ; Lindner, Jonathan ; Pizarro, Theresa T. / Targeting mucosal addressin cellular adhesion molecule (MAdCAM)-1 to noninvasively image experimental Crohn's disease. In: Gastroenterology. 2006 ; Vol. 130, No. 1. pp. 8-16.
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AU - Rivera-Nieves, Jesus

AU - Cominelli, Fabio

AU - Ley, Klaus F.

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