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• W2155176844 abstract "Macrophage infiltration is a common characteristic feature of atherosclerotic-vulnerable plaques. Macrophages recognize phosphatidylserine (PS) exposed on the surface of apoptotic cells, which triggers the engulfment of the apoptotic cells by macrophages through phagocytosis. In this study, we prepared radiolabeled PS liposomes for detection of vulnerable plaques.PS liposomes were prepared by lipid film hydration. Phosphatidylcholine (PC) liposomes were prepared as controls. Liposomes (100 or 200 nm) were generated by an extruder to produce PS100, PS200, PC100, and PC200 liposomes. These were then radiolabeled by encapsulating (111)In-nitrilotriacetic acid using an active-loading method. (111)In liposomes were incubated with cultured macrophages for 2 h, and the uptake level was measured. For biodistribution studies, the (111)In liposomes were injected intravenously into ddY mice. In addition, the (111)In liposomes were injected into apolipoprotein E-deficient (apoE-/-) mice, and the aortas were harvested for autoradiography and oil red O staining. For SPECT imaging, (111)In liposomes were injected intravenously into Watanabe heritable hyperlipidemic rabbits and scanned 48 h after injection.The radiochemical yields were greater than 95% for all the prepared (111)In liposomes. The level of in vitro uptake by macrophages was 60.5, 14.7, 32.0, and 14.4 percentage injected dose per milligram of protein for (111)In-PS100, (111)In-PC100, (111)In-PS200, and (111)In-PC200, respectively. In biodistribution studies, high spleen uptake was seen with PC liposomes. Liver uptake was high for all liposomes but was lowest with (111)In-PS200. The blood half-lives were 3.2, 22.0, 3.6, and 7.4 min for (111)In-PS100, (111)In-PC100, (111)In-PS200, and (111)In-PC200, respectively. The distribution of (111)In-labeled PS liposomes into atherosclerotic regions determined by autoradiography was well matched with the results of oil red O staining in apoE-/- mice. The target-to-nontarget ratios were 2.62, 2.23, 3.27, and 2.51 for (111)In-PS100, (111)In-PC100, (111)In-PS200, and (111)In-PC200, respectively. The aorta was successfully visualized by SPECT at 48 h after (111)In-labeled PS liposome injection; however, high liver uptake was also observed.From the in vitro uptake study, it has been demonstrated that macrophage targeting was accomplished by PS modification. Also, an atherosclerotic region was successfully detected by (111)In-PS200 in apoE-/- mice and Watanabe heritable hyperlipidemic rabbits in vivo. Liposome modification to obtain slower blood clearance and lower liver uptake would be required to improve the SPECT images." @default.
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• W2155176844 date "2013-12-12" @default.
• W2155176844 modified "2023-10-05" @default.
• W2155176844 title "Development of¹¹¹In-Labeled Liposomes for Vulnerable Atherosclerotic Plaque Imaging" @default.
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• W2155176844 doi "https://doi.org/10.2967/jnumed.113.123158" @default.
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