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Title:

Vasculitis: molecular imaging by targeting the inflammatory enzyme myeloperoxidase.

Document type:
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Author(s):
Su, HS; Nahrendorf, M; Panizzi, P; Breckwoldt, MO; Rodriguez, E; Iwamoto, Y; Aikawa, E; Weissleder, R; Chen, JW
Abstract:
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.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.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.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.
Journal title abbreviation:
Radiology
Year:
2012
Journal volume:
262
Journal issue:
1
Pages contribution:
181-90
Language:
eng
Fulltext / DOI:
doi:10.1148/radiol.11110040
Pubmed ID:
http://view.ncbi.nlm.nih.gov/pubmed/22084204
Print-ISSN:
0033-8419
TUM Institution:
Fachgebiet Neuroradiologie (Prof. Zimmer)
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