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Radiology. 2012 Jan;262(1):181-90. doi: 10.1148/radiol.11110040. Epub 2011 Nov 14.

Vasculitis: molecular imaging by targeting the inflammatory enzyme myeloperoxidase.

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  • 1Center for Molecular Imaging Research, Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Abstract

PURPOSE:

To determine if a molecular imaging approach targeting the highly oxidative enzyme myeloperoxidase (MPO) can help noninvasively identify and confirm sites of vascular wall inflammation in a murine model of vasculitis.

MATERIALS AND METHODS:

Animal experiments were approved by the institutional animal care committee. Twenty-six mice were studied, including eight MPO-deficient and six sham-operated mice as controls. Vasculitis was induced with intraperitoneal injection of Candida albicans water-soluble fraction (CAWS). Aortic root magnetic resonance imaging was performed after intravenous injection of the activatable MPO sensor (bis-5-hydroxytryptamide-diethylenetriaminepentatacetate gadolinium) (n = 23), referred to as MPO-Gd, or gadopentetate dimeglumine (n = 10). Seven mice were randomly assigned to receive either MPO-Gd or gadopentetate dimeglumine first. Aortic root specimens were collected for biochemical and histopathologic analyses to validate imaging findings. Statistical significance was calculated for contrast-to-noise ratios (CNRs) by using the paired t test.

RESULTS:

In the aortic root, the mean MPO-Gd CNRs after agent injection (CNR = 28.1) were more than 2.5-fold higher than those of sham-operated mice imaged with MPO-Gd and vasculitis mice imaged with gadopentetate dimeglumine (CNR = 10.6) (P < .05). MPO-Gd MR imaging helped identify areas of vasculitis that were not seen at unenhanced and contrast material-enhanced imaging with gadopentetate dimeglumine. Histopathologic and biochemical analyses for MPO and myeloid cells confirmed imaging findings. In MPO-deficient mice, injection of CAWS did not result in a vasculitis phenotype, implying a key role of the imaging target in disease cause.

CONCLUSION:

Molecular imaging targeting MPO can be a useful biomarker to noninvasively detect and confirm inflammation in vasculitis by using a murine model of Kawasaki disease.

© RSNA, 2011.

PMID:
22084204
[PubMed - indexed for MEDLINE]
PMCID:
PMC3244672
Free PMC Article
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