Noninvasive Detection of Macrophages in Atheroma Using a Radiocontrast-Loaded Phosphatidylserine-Containing Liposomal Contrast Agent for Computed Tomography

Purpose Macrophage plays an important role in plaque destabilization in atherosclerosis. By harnessing the affinity of macrophages to certain phospholipid species, a liposomal contrast agent containing phosphatidylserine (PS) and X-ray computed tomographic (CT) contrast agent was prepared and evaluated for CT imaging of plaque-associated macrophages in rabbit models of atherosclerosis. Procedures Liposomes containing PS and iodixanol were evaluated for their physicochemical characteristics, in vitro macrophage uptake, in vivo blood pool clearance, and organ distribution. Plaque enhancement in the aorta was imaged with CT in two atherosclerotic rabbit models. Results In vitro macrophage uptake of PS liposomes increased with increasing amount of PS in the liposomes. Overall clearance of PS liposomes was more rapid than control liposomes. Smaller PS liposomes ( d = 112 ± 4 nm) were more effective than control liposomes of similar size or larger control and PS liposomes ( d = 172 ± 17 nm) in enhancing aortic plaques in both rabbit models. Conclusions Proper liposomal surface modification and appropriate sizing are important determinant for CT-based molecular imaging of macrophages in atheroma.