Abstract 587: Diet Intervention Reduces 18F-galacto-RGD Uptake in Mouse Atherosclerotic Plaques
Objectives: Expression of αvβ3 integrin receptors by macrophages and endothelial cells has been proposed as a potential target for molecular imaging of vascular inflammation. We evaluated whether diet intervention reduces uptake of 18F-galacto-RGD, a PET tracer binding to αvβ3 integrin, in mouse atherosclerotic plaques.
Methods: After 4 months on high-cholesterol diet 28 LDLR/ApoB48 double knockout mice were randomized to either high-cholesterol diet (cholesterol group) or regular mouse chow (intervention group) for 3 months. The mice were injected with 700μCi of 18F-galacto-RGD and 100μCi of 3H-deoxyglucose followed by imaging with a small animal PET/CT scanner. The aortas were dissected, frozen and sectioned 2 hours after injection for analysis of biodistribution, autoradiography and histology.
Results: The same number of mice in the cholesterol (n=8) and intervention (n=8) groups completed the study protocol. Diet intervention reduced cholesterol levels. In vivo imaging showed 18F-galacto-RGD signals co-localizing with atherosclerotic aortic arch. Compared with the cholesterol group, %ID/g of 18F-galacto-RGD in the dissected aorta was lower in the intervention group (0.23±0.04 vs. 0.16±0.05, p<0.01) being comparable to healthy controls. Autoradiography showed focal uptake of 18F-galacto-RGD in atherosclerotic plaques that was lower in the intervention than cholesterol group (PSL/mm2 49±15 vs. 76±14, p<0.01). 18F-galacto-RGD uptake correlated with 3H-deoxyglucose accumulation in the same atherosclerotic plaques (p<0.01). In the normal vessel wall, uptake of 18F-galacto-RGD was comparable between groups. Compared with the cholesterol group, plaques in the intervention group showed comparable proportions of fibrosis and lipid, but significantly lower density of cells, mainly macrophages (p<0.01). Uptake of 18F-galacto-RGD correlated with density of cells in plaques (p<0.01).
Conclusions: Diet intervention reduced inflammation and uptake of 18F-galacto-RGD in mouse atherosclerotic plaques. These ex vivo results suggest that 18F-galacto-RGD is potentially suitable tracer for evaluation of therapies aimed at reduction of atherosclerotic plaque inflammation.