Uptake of (68)gallium in atherosclerotic plaques in LDLR(-/-)ApoB(100/100 )mice

BACKGROUND: 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 purpose of this study was to explore the uptake of (68)gallium ((68)Ga) in atherosclerotic plaques in mice. METHODS: Uptake of ionic (68)Ga was investigated in atherosclerotic LDLR(-/-)ApoB(100/100 )and C57BL/6N control mice at 3 h after injection. The ex vivo biodistribution of the (68)Ga was assessed and autoradiography of aortic cryosections was defined. In vivo imaging of (68)Ga was performed using a small animal positron emission tomography PET/CT scanner. RESULTS: Our results revealed that the uptake of (68)Ga-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. CONCLUSIONS: We observed a moderate but significantly elevated (68)Ga-radioactivity uptake in the aortic plaques of atherosclerotic mice, especially at the sites rich in macrophages. While the uptake of (68)Ga was promising in this animal model, the slow blood clearance may limit the usability of (68)Ga as a PET tracer for clinical imaging of atherosclerotic plaques.