Effect of pioglitazone on inflammation and calcification in atherosclerotic rabbits : An 18F-FDG-PET/CT in vivo imaging study.

Background: We developed an atherosclerotic rabbit model and tested pioglitazone as a drug intervention for early vascular calcification. Positron emission tomography/computed tomography (PET/CT) was used to evaluate inflammation and therapeutic effects.

Methods: We randomly divided 20 male New Zealand white rabbits into a pioglitazone-treated group (n = 10) and a control group (n = 10). Atherosclerosis was induced via a high-cholesterol diet and endothelial denudation. The animals were maintained on a hyperlipidemic diet for 16 weeks after surgery, and the treatment group received pioglitazone daily. Serum samples were obtained at 8 and 18 weeks postoperatively to assess high-sensitivity C‑reactive protein (hs-CRP) and matrix metalloproteinase-9 (MMP-9) concentrations. Sixteen rabbits underwent a mid-stage PET/CT scan at week 8, and 11 rabbits underwent an end-stage PET/CT scan at week 18. PET/CT parameters, including the mean standardized uptake value (SUVmean) and maximum standardized uptake value (SUVmax), were measured and documented.

Results: There were significantly lower hs-CRP and MMP-9 levels in the pioglitazone group at week 18 (p < 0.01). At the end of the 8th week, no significant between-group differences in SUVmean and SUVmax were observed. From week 8 to week 18, the SUVmean and SUVmax decreased in the pioglitazone group but the SUVmean increased in the control group, with significant between-group differences at the end of the 18th week (p < 0.01). Histopathological examination of aortas in the control and pioglitazone groups revealed significantly smaller plaque area, macrophage density, and tissue calcification area in the latter group.

Conclusions: Pioglitazone affects early vascular microcalcification, and pioglitazone-induced changes can be assessed using 18F-FDG-PET/CT.