Diet intervention reduces uptake of αvβ3 integrin-targeted PET tracer 18F-galacto-RGD in mouse atherosclerotic plaques

Abstract

BackgroundExpression of αvβ3 integrin has been proposed as a marker for atherosclerotic lesion inflammation. We studied whether diet intervention reduces uptake of αvβ3 integrin-targeted positron emission tomography tracer 18F-galacto-RGD in mouse atherosclerotic plaques. Methods and ResultsHypercholesterolemic LDLR−/− ApoB100/100 mice on high-fat diet for 4 months were randomized to further 3 months on high-fat diet (high-fat group, n = 8) or regular mouse chow (intervention group, n = 7). Intima-media ratio describing plaque burden was comparable between intervention and high-fat groups (2.0 ± 0.5 vs 2.3 ± 0.8, P = .5). Uptake of 18F-galacto-RGD in the aorta was lower in the intervention than high-fat group (%ID/g 0.16 vs 0.23, P < .01). Autoradiography showed 35% lower uptake of 18F-galacto-RGD in the atherosclerotic plaques in the intervention than high-fat group (P = .007). Uptake of 18F-galacto-RGD in plaques correlated with uptake of 3H-deoxyglucose and nuclear density, which was lower in the intervention than high-fat group (P = .01). Flow cytometry demonstrated macrophages expressing αv and β3 integrins in the aorta. ConclusionsUptake of 18F-galacto-RGD in mouse atherosclerotic lesions was reduced by lipid-lowering diet intervention. Expression of αvβ3 integrin is a potential target for evaluation of therapy response in atherosclerosis.