Abstract 12061: Insights Into CT Contrast Uptake by Atheroma-Associated Macrophages in Hyperlipidemic Rabbits
Introduction: Visualization of macrophage activities and distribution may provide useful insight into plaque vulnerability.
Hypothesis: Uptake of phosphatidylserine (PS)-coated liposomes by macrophages in the arterial wall will generate contrast enhancement for CT imaging.
Methods: Efficient loading of liposomes was accomplished by a modified ethanol vaporization method. Pharmacokinetic parameters and tissue distribution of liposomes were evaluated in mice and New Zealand White (NZW) rabbits. Both Watanabe Hereditary Hyperlipidemic (WHHL) and balloon-denuded cholesterol-fed NZW rabbits were injected with control and PS-liposomes, and imaged 48 hours later with a flat-panel CT scanner. Image processing and reconstruction were performed to demonstrate contrast enhancement in the aorta. Immunohistochemical and immunofluorescence microscopy were used to characterize contrast uptake in relation to macrophage distribution.
Results: Iodixanol in liposomes ranged from 65 to 80 mg/ml. In vitro liposomal uptake by macrophages increased with increasing percentage of PS in the liposomes and cell viability was unaffected up to 20% PS. Liposomally encapsulated iodixanol prolonged blood pool enhancement up to 4h after injection and diverted its clearance to the reticuloendothelial system. Only the 100nm PS-liposomes generated specific aortic wall enhancement in association with atheroma. Histological examination revealed diffused non-specific retention of 100nm control liposomes and the absence of 200 nm control and PS-liposomes in the aortic wall. Only 100nm PS-liposomes specifically co-localized with plaque-associated macrophages in both rabbit models.
Conclusions: In vivo uptake of CT contrast by plaque-associated macrophages is dependent on liposome size and surface modifications. Molecular imaging of macrophage retention of CT contrast is feasible with sufficient payload in the liposomal carrier.
Author Disclosures: D. Danila: Research Grant; Significant; AHA, NIH. V. Bagalkot: None. P. Kee: Research Grant; Modest; AHA. Research Grant; Significant; NIH.
- © 2014 by American Heart Association, Inc.