Molecular imaging of endothelial activation and mineralization in a mouse model of accelerated atherosclerosis

PURPOSE: Preclinical imaging of endothelial activation and mineralization using both positron emission tomography (PET) and magnetic resonance (MR) remains scarce. PROCEDURES: A group of uremic ApoE(−/−) (Ur), non-uremic ApoE(−/−) (NUr), and control C57Bl/6 J mice (Ctl) were investigated. Mineralization process was assessed using sodium fluoride ([18F]NaF) PET, and MR imaging combined with intravenous injection of MPIO-αVCAM-1 was used to evaluate endothelial activation. Micro- and macrocalcifications were evaluated by flame atomic absorption spectroscopy and von Kossa staining, respectively. RESULTS: Ur mice showed an active and sustained mineralization process compared to Ctl mice (p = 0.002) using [18F]NaF PET imaging. Calcium plasma level was increased in Ur (2.54 ± 0.09 mM, n = 17) compared to NUr and Ctl mice (2.24 ± 0.01, n = 22, and 2.14 ± 0.02, n = 27, respectively; p < 0.0001). Likewise, vascular calcium content was increased in Ur (0.51 ± 0.06 μg Ca(2+) per milligram of dry weight aorta, n = 11) compared to NUr (0.27 ± 0.05, n = 9, p = 0.013) and Ctl (0.28 ± 0.05, n = 11, p = 0.014). Ur mice also had a higher inflammatory state using MPIO-αVCAM-1 MR (p global = 0.01, post hoc analysis Ur vs. Ctl p = 0.003) associated with increased VCAM-1 expression (p global = 0.02). Aortic remodeling at the level of the brachiocephalic trunk, brachiocephalic trunk itself, and aortic arch in Ur mice was also demonstrated using MR. CONCLUSIONS: Preclinical molecular imaging allowed in vivo characterization of the early phase of atherosclerosis. [18F]NaF PET showed early and sustained vascular mineralization in uremic ApoE(−/−) mice. MPIO-αVCAM-1 MR imaging demonstrated aortic endothelial activation, predominantly in segments with vascular remodeling.