Assessment of Global Cardiac Uptake of Radiolabeled Iron Oxide Nanoparticles in Apolipoprotein-E-Deficient Mice: Implications for Imaging Cardiovascular Inflammation

Abstract

Atherosclerosis is a leading cause of death in industrialized countries and is characterized by the accumulation of lipids and inflammatory cells, including macrophages, in blood vessel walls. Therefore, the ability to image macrophages could help identify plaques that are precursors of acute thrombotic events. Previous research has shown that long-circulating nanoparticles could be used to detect macrophages within atherosclerotic plaques of the aorta. By conducting this study, we investigated whether global cardiac uptake of radiolabeled nanoparticles could allow assessment of total macrophage burden in the coronary arteries. Dextran-coated iron oxide nanoparticles (IONPs) were labeled with iodine-125 via Bolton-Hunter (sulfosuccinimidyl-3-[4-hydroxyphenyl]propionate) method. IONPs were characterized by means of dynamic light scattering and transmission electronic microscopy. Biodistribution studies were performed in healthy and atherosclerotic mice. Additionally, digital autoradiography of hearts from both healthy and atherosclerotic mice was performed to assess regional and global atherosclerotic burden. The [(125)I]IONPs exhibited high radiolabel stability and long blood circulation, which eventually led to high heart uptake in apoE -/- mice when compared with healthy controls. Furthermore, digital autoradiography showed substantially enhanced emission of signals from the hearts of atherosclerotic mice, while no or minimal cardiac signals were detected in healthy mice. This preparation showed adequate physical-chemical properties for in vivo studies, such as small size (∼30 nm), good radiolabel stability, and long circulation time. There was also significant accumulation in the heart of apoE-/- mice compared with that of healthy control animals. These findings suggest that radiolabeled dextran-coated iron oxide nanoparticles may have potential to become a useful tool to detect macrophages in the atherosclerosis plaques of coronary arteries; however, these preliminary findings should be confirmed by further studies in a larger scale in various atherosclerosis models.