Abstract 572: Non-invasive Multimodality Assessment of Vascular Effects of the PPAR-gamma Agonist-Pioglitazone
Introduction. Macrophages are the main inflammatory effector-cells in atherosclerotic plaque and are believed to be a major contributor to plaque instability and rupture. Pioglitazone, a PPAR-γ-agonist, has been shown to delay the progression of atherosclerosis in mouse models and exhibits positive effects on survival in high risk populations in humans. Pioglitazone displays its positive effects mainly through anti-inflammatory actions on macrophages, promotion of reversal cholesterol transport and positive effects on lipoprotein profiles.
Aim. The development of sensitive non-invasive imaging techniques for analyzing plaque inflammation can be a valuable tool for analyzing effectiveness of therapeutic interventions. Our aim in this study was to use FDG-PET/CT to monitor changes in inflammation in atherosclerotic plaque after Pioglitazone treatment and to delineate anatomical changes with multi-contrast MRI.
Methods. 13 atherosclerotic New Zealand White rabbits underwent FDG-PET/CT imaging to determine Standard Uptake Values (SUV= PET activity concentration/(decay corrected dose/body weight) and multicontrast (T1, T2 and PD) MRI. After imaging, rabbits were divided into a control- (n= 7) and treatment group (n= 6). The control group maintained a high cholesterol diet while the treatment group received 10mg/kg Pioglitazone admixed to it. Both groups were imaged again after 1 and 3 months. At 3 months all animals were sacrificed. Results. At baseline, the abdominal aorta of both groups showed no significant differences in maximal SUV (SUVmax) as determined by FDG-PET/CT (0.63 vs 0.63, p= 0.97). At 1 month, the treatment group showed decreasing SUVmax values whereas controls showed a further increase (0.58 vs 0.70, p= 0.01). This trend continued at 3 month (0.56 vs 0.74, p= 0.003). In contrast, no significant change in vessel wall area was detected with MRI over the entire period between both groups. Macrophage staining revealed a significant decrease of macrophage content at 3 month upon Piogliatzone treatment and this was accompanied with a significant increase in collagen content.
Conclusion: FDG-PET/CT successfully detected changes in vessel wall inflammation and macrophage content as early as one month upon Pioglitazone treatment.