Abstract 145: Development of Radiolabeled Liposomes for Atherosclerotic Plaque Imaging

Abstract

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 111 In-NTA using active-loading method. The 111 In-liposomes were incubated with mouse peritoneum macrophages for 2hr and uptake level was investigated. For biodistribution study, 111 In-liposomes were intravenously injected to ddY mice. Also, the 111 In-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 111 In-PS100, 111 In-PC100, 111 In-PS200, 111 In-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 111 In-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 111 In-PS200. The aorta was successfully visualized by SPECT at 48hr after the 111 In-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 111 In-PS200 in apoE-/- mice and WHHL rabbits in vivo .