Abstract 2195: Non-Invasive Imaging of Atherosclerotic Lesions in Apolipoprotein E-Deficient and Low Density Lipoprotein Receptor-Deficient Mice With Annexin A5
Background Non-invasive imaging of atherosclerosis in apolipoprotein E-deficient (apoE−/−) and low density lipoprotein receptor-deficient (LDLR−/−) mice would greatly enhance our ability to study the natural history of atherosclerosis. We evaluated the feasibility of annexin A5 imaging for the detection of inflammation.
Methods A total of 33 mice were used. Of these 33 mice, apoE−/− mice with (n = 5) and without (n = 8) cholesterol diet and LDLR−/− mice with (n = 7) and without (n = 7) cholesterol diet were compared with 6 normal wild type (C57BL/6) mice with the same genetic background. 99mTc-annexin A5 was injected in 31 animals for noninvasive imaging using micro-SPECT/CT imaging. Aotras were explanted for ex vivo images and percent injected dose per gram (%ID/g) annexin uptake. Histological and immunohistochemical characteristics were also evaluated. For the evaluation of localization of annexin A5, biotinylated annexin A5 was injected in the remaining 2 normally fed apoE−/− mice.
Results Aortic lesions were clearly visualized non-invasively by micro-SPECT and aorta calcification was detectable by micro-CT. The quantitative uptake of 99mTc-annexin A5 was highest in cholesterol-fed apoE−/− (%ID/g: 0.88 ± 0.27%), followed by normal chow-fed apoE−/− (0.60 ± 0.16%), cholesterol-fed LDLR−/− (0.59 ± 0.14%), chow-fed LDLR−/− (0.40 ± 0.31%), and control (0.15 ± 0.05%) mice. Histological extent of atherosclerosis paralleled radiotracer findings, and immunohistochemical studies revealed a significant correlation between 99mTc-annexin A5 uptake and both macrophage infiltration and the extent of apoptosis. Intravenously-injected biotinylated annexin A5 localized in apoptotic and non-apoptotic macrophages.
Conclusions The present study demonstrates the feasibility of non-invasive imaging of atherosclerosis with radiolabeled annexin A5 in accepted mouse models of human atherosclerosis and paves the way for longitudinal intervention studies.