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  • Title: Evaluation of alphavbeta3 integrin-targeted positron emission tomography tracer 18F-galacto-RGD for imaging of vascular inflammation in atherosclerotic mice.
    Author: Laitinen I, Saraste A, Weidl E, Poethko T, Weber AW, Nekolla SG, Leppänen P, Ylä-Herttuala S, Hölzlwimmer G, Walch A, Esposito I, Wester HJ, Knuuti J, Schwaiger M.
    Journal: Circ Cardiovasc Imaging; 2009 Jul; 2(4):331-8. PubMed ID: 19808614.
    Abstract:
    BACKGROUND: (18)F-Galacto-RGD is a positron emission tomography (PET) tracer binding to alpha(v)beta(3) integrin that is expressed by macrophages and endothelial cells in atherosclerotic lesions. Therefore, we evaluated (18)F-galacto-RGD for imaging vascular inflammation by studying its uptake into atherosclerotic lesions of hypercholesterolemic mice in comparison to deoxyglucose. METHODS AND RESULTS: Hypercholesterolemic LDLR(-/-)ApoB(100/100) mice on a Western diet and normally fed adult C57BL/6 control mice were injected with (18)F-galacto-RGD and (3)H-deoxyglucose followed by imaging with a small animal PET/CT scanner. The aorta was dissected 2 hours after tracer injection for biodistribution studies, autoradiography, and histology. Biodistribution of (18)F-galacto-RGD was higher in the atherosclerotic than in the normal aorta. Autoradiography demonstrated focal (18)F-galacto-RGD uptake in the atherosclerotic plaques when compared with the adjacent normal vessel wall or adventitia. Plaque-to-normal vessel wall ratios were comparable to those of deoxyglucose. Although angiogenesis was not detected, (18)F-galacto-RGD uptake was associated with macrophage density and deoxyglucose accumulation in the plaques. Binding to atherosclerotic lesions was efficiently blocked in competition experiments. In vivo imaging visualized (18)F-galacto-RGD uptake colocalizing with calcified lesions of the aortic arch as seen in CT angiography. CONCLUSIONS: (18)F-Galacto-RGD demonstrates specific uptake in atherosclerotic lesions of mouse aorta. In this model, its uptake was associated with macrophage density. (18)F-Galacto-RGD is a potential tracer for noninvasive imaging of inflammation in atherosclerotic lesions.
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