Evaluation of α_vβ₃ integrin-targeted positron emission tomography tracer ¹⁸F-galacto-RGD for imaging of vascular inflammation in atherosclerotic mice

¹⁸F-Galacto-RGD is a positron emission tomography (PET) tracer binding to α_vβ₃ integrin that is expressed by macrophages and endothelial cells in atherosclerotic lesions. Therefore, we evaluated ¹⁸F-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 ^-1-ApoB^100/100 mice on a Western diet and normally fed adult C57BL/6 control mice were injected with ¹⁸F-galacto-RGD and ³H-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 ¹⁸F-galacto-RGD was higher in the atherosclerotic than in the normal aorta. Autoradiography demonstrated focal ¹⁸F-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, ¹⁸F-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 ¹⁸F-galacto-RGD uptake colocalizing with calcified lesions of the aortic arch as seen in CT angiography. Conclusions-¹⁸F-Galacto-RGD demonstrates specific uptake in atherosclerotic lesions of mouse aorta. In this model, its uptake was associated with macrophage density. ¹⁸F-Galacto-RGD is a potential tracer for noninvasive imaging of inflammation in atherosclerotic lesions.