title: Pioglitazone modulates vascular inflammation in atherosclerotic rabbits noninvasive assessment with FDG-PET-CT and dynamic contrast-enhanced MR imaging.
abstract: OBJECTIVE
  We sought to determine the antiatherosclerotic properties of pioglitazone using multimethod noninvasive imaging techniques.
  
  
  BACKGROUND
  Inflammation is an essential component of vulnerable or high-risk atheromas. Pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist, possesses potent anti-inflammatory properties. We aimed to quantify noninvasively the anti-inflammatory effects of pioglitazone on atheroma using (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI).
  
  
  METHODS
  Atherosclerotic plaques were induced in the aorta of 15 New Zealand white rabbits by a combination of a hyperlipidemic diet and 2 balloon endothelial denudations. Nine rabbits continued the same diet, whereas 6 rabbits received pioglitazone (10 mg/kg orally) in addition to the diet. Twelve animals underwent (18)F-FDG-PET/CT, and 15 animals underwent DCE-MRI at baseline, 1 month, and 3 months after treatment initiation. Concomitantly, serum metabolic parameters were monitored. After imaging was completed, aortic histologic analysis and correlation analysis were performed.
  
  
  RESULTS
  The (18)F-FDG-PET/CT imaging detected an increase in average standardized uptake value in the control group (p < 0.01), indicating progressive inflammation, whereas stable standardized uptake values were observed in the treatment group, indicating no progression. The DCE-MRI analysis detected a significant decrease in the area under the curve for the pioglitazone group (p < 0.01). Immunohistologic examination of the aortas demonstrated a significant decrease in macrophage and oxidized phospholipid immunoreactivity in the pioglitazone group (p = 0.04 and p = 0.01, respectively) with respect to control animals, underlining the imaging results. Serum metabolic parameters showed no difference between groups. Strong positive correlations between standardized uptake value and macrophage density and between area under the curve and neovessels were detected (r(2) = 0.86 and p < 0.0001, and r(2) = 0.66 and p = 0.004, respectively).
  
  
  CONCLUSIONS
  Both (18)F-FDG-PET/CT and DCE-MRI demonstrate noninvasively the anti-inflammatory effects of pioglitazone on atheroma. Both imaging methods seem suited to monitor inflammation in atherosclerosis.
authors: Translational and Molecular Imaging Institute, Imaging Science Laboratories, Mount Sinai School of Medicine, New York, New York, USA.
authors: Esad
authors: E
authors: Vucic
authors: Stephen D
authors: SD
authors: Dickson
authors: Claudia
authors: C
authors: Calcagno
authors: James H F
authors: JH
authors: Rudd
authors: Erin
authors: E
authors: Moshier
authors: Katsumi
authors: K
authors: Hayashi
authors: Jessica S
authors: JS
authors: Mounessa
authors: Michelle
authors: M
authors: Roytman
authors: Matthew J
authors: MJ
authors: Moon
authors: James
authors: J
authors: Lin
authors: Sotirios
authors: S
authors: Tsimikas
authors: Edward A
authors: EA
authors: Fisher
authors: Klaas
authors: K
authors: Nicolay
authors: Valentin
authors: V
authors: Fuster
authors: Zahi A
authors: ZA
authors: Fayad
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001011:Aorta / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D001027:Aortography; D050197:Atherosclerosis / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D003287:Contrast Media; D004195:Disease Models, Animal; D018450:Disease Progression; D019788:Fluorodeoxyglucose F18; D007150:Immunohistochemistry; D007249:Inflammation / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D008055:Lipids / Q000097:blood; D008264:Macrophages / Q000473:pathology; D018810:Magnetic Resonance Angiography; D064847:Multimodal Imaging; D009389:Neovascularization, Pathologic / Q000175:diagnosis / Q000188:drug therapy; D047495:PPAR gamma / Q000819:agonists; D000077205:Pioglitazone; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D011817:Rabbits; D019275:Radiopharmaceuticals; D045162:Thiazolidinediones / Q000494:pharmacology*; D013997:Time Factors; D014057:Tomography, X-Ray Computed
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D003287:Contrast Media; D008055:Lipids; D047495:PPAR gamma; D019275:Radiopharmaceuticals; D045162:Thiazolidinediones; D019788:Fluorodeoxyglucose F18; D000077205:Pioglitazone