Abstract 145: Development of Radiolabeled Liposomes for Atherosclerotic Plaque Imaging
Objectives Molecular imaging enables non-invasive in vivo detection of vulnerable plaques. Macrophage infiltration is characteristics for atherosclerotic vulnerable plaques, and many apoptotic cells are seen in this region. Also, it is known that macrophages recognize phosphatidylserine (PS) that is exposed on the cell surface during apoptosis to phagocytize these cells. In this study, we prepared radiolabeled phosphatidylserine liposomes for detection of vulnerable plaques.
Methods PS liposomes and control liposomes (phosphatidylcholine (PC) liposomes) were prepared by lipid film hydration. The prepared sizes were 100 nm and 200 nm (PS100, PS200, PC100, and PC200 liposomes). The liposomes were radiolabeled by encapsulating 111In-NTA using active-loading method. The 111In-liposomes were incubated with mouse peritoneum macrophages for 2hr and uptake level was investigated. For biodistribution study, 111In-liposomes were intravenously injected to ddY mice. Also, the 111In-liposomes were injected to apoE -/- mice, and the aortas were harvested for autoradiography and Oil-Red O staining. For SPECT imaging, WHHL rabbits were used.
Results The in vitro uptake levels to macrophages were 60.5, 14.7, 32.0, 14.4 %dose/mg protein, for 111In-PS100, 111In-PC100, 111In-PS200, 111In-PC200, respectively. The liver uptake was high in all liposomes, and blood clearance was faster in PS liposomes than PC liposomes. The in vivo distributions of 111In-labeled PS liposomes to atherosclerotic regions were well matched with Oil-Red O staining in apoE -/- mouse. Target-to-non-target ratio was highest in 111In-PS200. The aorta was successfully visualized by SPECT at 48hr after the 111In-labeled PS liposome injection.
Conclusions By in vitro uptake study, it is revealed that macrophage targeting was accomplished by PS. Also, atherosclerotic region was successfully detected by 111In-PS200 in apoE-/- mice and WHHL rabbits in vivo.
- © 2013 by American Heart Association, Inc.