title: Vasculitis: molecular imaging by targeting the inflammatory enzyme myeloperoxidase.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Molecular Imaging Research, Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Henry S
authors.initials: HS
authors.lastname: Su
authors.forename: Matthias
authors.initials: M
authors.lastname: Nahrendorf
authors.forename: Peter
authors.initials: P
authors.lastname: Panizzi
authors.forename: Michael O
authors.initials: MO
authors.lastname: Breckwoldt
authors.forename: Elisenda
authors.initials: E
authors.lastname: Rodriguez
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: Elena
authors.initials: E
authors.lastname: Aikawa
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.forename: John W
authors.initials: JW
authors.lastname: Chen
mesh_terms: D000818:Animals; D001011:Aorta / Q000201:enzymology* / Q000473:pathology*; D002465:Cell Movement; D002851:Chromatography, High Pressure Liquid; D003287:Contrast Media / Q000138:chemical synthesis; D019786:Gadolinium DTPA / Q000138:chemical synthesis; D007150:Immunohistochemistry; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D009080:Mucocutaneous Lymph Node Syndrome / Q000175:diagnosis* / Q000201:enzymology*; D009195:Peroxidase / Q000378:metabolism*; D011897:Random Allocation; D018709:Statistics, Nonparametric
chemical_list: D003287:Contrast Media; D009195:Peroxidase; D019786:Gadolinium DTPA
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