Abstract
BackgroundAtherosclerosis is a chronic inflammatory disease of artery wall characterized by infiltration of monocytes into subendothelial space and their differentiation into macrophages. Since rupture-prone plaques commonly contain high amounts of activated macrophages, imaging of the macrophage content may provide a useful tool for the evaluation of plaque vulnerability. The purpose of this study was to explore the uptake of 68gallium (68Ga) in atherosclerotic plaques in mice.MethodsUptake of ionic 68Ga was investigated in atherosclerotic LDLR-/-ApoB100/100 and C57BL/6N control mice at 3 h after injection. The ex vivo biodistribution of the 68Ga was assessed and autoradiography of aortic cryosections was defined. In vivo imaging of 68Ga was performed using a small animal positron emission tomography PET/CT scanner.ResultsOur results revealed that the uptake of 68Ga-radioactivity was higher in atherosclerotic plaques than in healthy vessel wall (ratio 1.8 ± 0.2, p = 0.0002) and adventitia (ratio 1.3 ± 0.2, p = 0.0011). The autoradiography signal co-localized with macrophages prominently as demonstrated by Mac-3 staining. In both mice strains, the highest level of radioactivity was found in the blood.ConclusionsWe observed a moderate but significantly elevated 68Ga-radioactivity uptake in the aortic plaques of atherosclerotic mice, especially at the sites rich in macrophages. While the uptake of 68Ga was promising in this animal model, the slow blood clearance may limit the usability of 68Ga as a PET tracer for clinical imaging of atherosclerotic plaques.
Highlights
Atherosclerosis is a chronic inflammatory disease of artery wall characterized by infiltration of monocytes into subendothelial space and their differentiation into macrophages
Since the rupture-prone plaques commonly contain high amounts of activated macrophages, imaging of the macrophages may provide a useful tool for determining plaque vulnerability [1,2,3,4,5]. 68Gallium (68Ga, T1/2 68 min) is a generator-produced, positron-emitting radionuclide with a high positron yield (89%) possessing suitable physical properties for in vivo PET imaging. 67Gallium (67Ga) has traditionally been used to image inflammation with gamma cameras
Characterization of atherosclerotic plaques After 3 to 4 months on a Western-type diet, the LDLR-/ApoB100/100 mice had developed areas covered with atherosclerotic plaques in aortic arch, aortic arteries, and in the distal part of aorta
Summary
Atherosclerosis is a chronic inflammatory disease of artery wall characterized by infiltration of monocytes into subendothelial space and their differentiation into macrophages. Since rupture-prone plaques commonly contain high amounts of activated macrophages, imaging of the macrophage content may provide a useful tool for the evaluation of plaque vulnerability. The autoradiography signal co-localized with macrophages prominently as demonstrated by Mac-3 staining In both mice strains, the highest level of radioactivity was found in the blood. Conclusions: We observed a moderate but significantly elevated 68Ga-radioactivity uptake in the aortic plaques of atherosclerotic mice, especially at the sites rich in macrophages. Atherosclerosis is a chronic inflammatory disease of artery wall with infiltration of monocytes into subendothelial space and their differentiation into macrophages. Since the rupture-prone plaques commonly contain high amounts of activated macrophages, imaging of the macrophages may provide a useful tool for determining plaque vulnerability [1,2,3,4,5]. The aim of this study was to determine the uptake of ionic 68Ga in the atherosclerotic plaques in mice
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