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

Antti Saraste, Iina Laitinen, Eliane Weidl, Moritz Wildgruber, Axel W Weber, Stephan G Nekolla, Gabriele Hölzlwimmer, Irene Esposito, Axel Walch, Pia Leppänen, Irina Lisinen, Peter B Luppa, Seppo Ylä-Herttuala, Hans-Jürgen Wester, Juhani Knuuti, Markus Schwaiger
Journal of Nuclear Cardiology 2012, 19 (4): 775-84

BACKGROUND: Expression of α(v)β(3) integrin has been proposed as a marker for atherosclerotic lesion inflammation. We studied whether diet intervention reduces uptake of α(v)β(3) integrin-targeted positron emission tomography tracer (18)F-galacto-RGD in mouse atherosclerotic plaques.

METHODS AND RESULTS: Hypercholesterolemic LDLR(-/-) ApoB(100/100) 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 (18)F-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 (18)F-galacto-RGD in the atherosclerotic plaques in the intervention than high-fat group (P = .007). Uptake of (18)F-galacto-RGD in plaques correlated with uptake of (3)H-deoxyglucose and nuclear density, which was lower in the intervention than high-fat group (P = .01). Flow cytometry demonstrated macrophages expressing α(v) and β(3) integrins in the aorta.

CONCLUSIONS: Uptake of (18)F-galacto-RGD in mouse atherosclerotic lesions was reduced by lipid-lowering diet intervention. Expression of α(v)β(3) integrin is a potential target for evaluation of therapy response in atherosclerosis.

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