Author + information
- Received March 4, 2011
- Revision received April 22, 2011
- Accepted April 22, 2011
- Published online October 1, 2011.
- Esad Vucic, MD⁎,†,
- Stephen D. Dickson, MS⁎,
- Claudia Calcagno, MD, PhD⁎,‡,
- James H.F. Rudd, MD, PhD§,
- Erin Moshier, MS∥,
- Katsumi Hayashi, MD⁎,
- Jessica S. Mounessa, BS⁎,
- Michelle Roytman, BS⁎,
- Matthew J. Moon, BS⁎,
- James Lin, MS⁎,
- Sotirios Tsimikas, MD¶,
- Edward A. Fisher, MD, PhD#,
- Klaas Nicolay, PhD⁎⁎,
- Valentin Fuster, MD, PhD†,†† and
- Zahi A. Fayad, PhD⁎,†,‡,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Zahi A. Fayad, Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1234, New York, New York 10029
Objectives 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 18F-fluorodeoxyglucose (18F-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 18F-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 18F-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 (r2 = 0.86 and p < 0.0001, and r2 = 0.66 and p = 0.004, respectively).
Conclusions Both 18F-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.
- dynamic contrast-enhanced magnetic resonance imaging
- 18F-fluorodeoxyglucose positron emission tomography/computed tomography
This investigation was supported in part by an investigator-initiated grant from Takeda Pharmaceutical (to Dr. Vucic); the Fondation Leducq (to Dr. Tsimikas); grants R01 HL071021 and R01 HL078667 from the National Heart, Lung and Blood Institute, National Institutes of Health (to Dr. Fayad); and grant EB009638 from the NBIB (National Institute of Biomedical Imaging and Bioengineering), National Institutes of Health (to Dr. Fayad). Dr. Tsimikas holds patents on oxidation-specific antibodies through the University of California San Diego. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Mr. Dickson and Dr. Calcagno contributed equally to this work. H. William Strauss, MD, served as Guest Editor for this article.
- Received March 4, 2011.
- Revision received April 22, 2011.
- Accepted April 22, 2011.
- American College of Cardiology Foundation