Research ArticleImaging

Ultrasensitive molecular imaging of intestinal mucosal inflammation using leukocyte-mimicking particles targeted to MAdCAM-1 in mice

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Science Translational Medicine  09 Sep 2020:
Vol. 12, Issue 560, eaaz4047
DOI: 10.1126/scitranslmed.aaz4047

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Imaging intestinal inflammation

As an alternative to ileocolonoscopy with biopsy required to diagnose and monitor inflammatory bowel diseases, Fournier et al. investigated the use of magnetic resonance imaging with microsized particles of iron oxide targeting mucosal vascular addressin cell adhesion molecule 1 on inflamed mucosal tissues. They showed that the contrast agent bound to activated endothelium in the gastrointestinal tract and could be used to visualize inflammation in mouse models of colitis. Therapeutic response to atorvastatin or anti-TNF antibody could also be monitored using the contrast agent. Results support use of the molecular imaging for noninvasive diagnosis and monitoring of mucosal inflammation.

Abstract

Mucosal tissues play critical roles in health and disease as the primary barrier between the external world and the inner body, lining the digestive, respiratory, urinary, mammary, and reproductive tracts. Clinical evaluation of mucosal tissues is currently performed using endoscopy, such as ileocolonoscopy for the intestinal mucosa, which causes substantial patient discomfort and can lead to organ damage. Here, we developed a contrast agent for molecular magnetic resonance imaging (MRI) that is targeted to mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1), an adhesion molecule overexpressed by inflamed mucosal tissues. We investigated the diagnostic performance of molecular MRI of MAdCAM-1 to detect mucosal inflammation in several models of acute and chronic intestinal inflammation in mice. We demonstrated that molecular MRI of MAdCAM-1 reveals disease activity and can evaluate the response to inflammatory treatments along the whole intestinal mucosa in clinically relevant models of inflammatory bowel diseases. We also provide evidence that this technique can detect low, subclinical mucosal inflammation. Molecular MRI of MAdCAM-1 has potential applications in early diagnosis, longitudinal follow-up, and therapeutic response monitoring in diseases affecting mucosal tissues, such as inflammatory bowel diseases.

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