期刊
CIRCULATION-CARDIOVASCULAR IMAGING
卷 2, 期 4, 页码 331-338出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCIMAGING.108.846865
关键词
atherosclerosis; imaging; inflammation; plaque; radioisotopes
资金
- EC-FP6-project DiMI [LSHBCT-2005-512146]
- Academy of Finland Centre of Excellence in Molecular Imaging in Cardiovascular and Metabolic Research
- Finnish Foundation for Cardiovascular Research
- Instrumentarium Science Foundation
- Drug Discovery Graduate School
Background-F-18-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 F-18-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 F-18-galacto-RGD and H-3-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 F-18-galacto-RGD was higher in the atherosclerotic than in the normal aorta. Autoradiography demonstrated focal F-18-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, F-18-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 F-18-galacto-RGD uptake colocalizing with calcified lesions of the aortic arch as seen in CT angiography. Conclusions- F-18-Galacto-RGD demonstrates specific uptake in atherosclerotic lesions of mouse aorta. In this model, its uptake was associated with macrophage density. F-18-Galacto-RGD is a potential tracer for noninvasive imaging of inflammation in atherosclerotic lesions. (Circ Cardiovasc Imaging. 2009;2:331-338.)
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