ABSTRACT
PURPOSE: Oxidized low-density lipoprotein (oxLDL) plays a key role in endothelial dysfunction, vascular inflammation, and atherogenesis. The aim of this study was to assess blood clearance and in vivo kinetics of radiolabeled oxLDL in mice.METHODS: We synthesized ¹²³I-oxLDL by the iodine monochloride method, and performed an uptake study in CHO cells transfected with lectin-like oxLDL receptor-1 (LOX-1). In addition, we evaluated the consistency between the ¹²³I-oxLDL autoradiogram and the fluorescence image of DiI-oxLDL after intravenous injection for both spleen and liver. Whole-body dynamic planar images were acquired 10 min post injection of ¹²³I-oxLDL to generate regional time-activity curves (TACs) of the liver, heart, lungs, kidney, head, and abdomen. Regional radioactivity for those excised tissues as well as the bladder, stomach, gut, and thyroid were assessed using a gamma counter, yielding percent injected dose (%ID) and dose uptake ratio (DUR). The presence of ¹²³I-oxLDL in serum was assessed by radio-HPLC.RESULTS: The cellular uptakes of ¹²³I-oxLDL were identical to those of DiI-oxLDL, and autoradiograms and fluorescence images also exhibited consistent distributions. TACs after injection of ¹²³I-oxLDL demonstrated extremely fast kinetics. The radioactivity uptake at 10 min postinjection was highest in the liver (40.8 ± 2.4% ID). Notably, radioactivity uptake was equivalent throughout the rest of the body (39.4 ± 2.7% ID). HPLC analysis revealed no remaining ¹²³I-oxLDL or its metabolites in the blood.CONCLUSION: ¹²³I-OxLDL was widely distributed not only in the liver, but also throughout the whole body, providing insight into the pathophysiological effects of oxLDL.
Subject(s)
Animals , Cricetinae , Mice , Abdomen , Atherosclerosis , CHO Cells , Chromatography, High Pressure Liquid , Fluorescence , Head Kidney , Heart , Inflammation , Injections, Intravenous , Iodine , Kinetics , Lipoproteins , Liver , Lung , Methods , Radioactivity , Spleen , Stomach , Thyroid Gland , Urinary BladderABSTRACT
PURPOSE@#Oxidized low-density lipoprotein (oxLDL) plays a key role in endothelial dysfunction, vascular inflammation, and atherogenesis. The aim of this study was to assess blood clearance and in vivo kinetics of radiolabeled oxLDL in mice.@*METHODS@#We synthesized ¹²³I-oxLDL by the iodine monochloride method, and performed an uptake study in CHO cells transfected with lectin-like oxLDL receptor-1 (LOX-1). In addition, we evaluated the consistency between the ¹²³I-oxLDL autoradiogram and the fluorescence image of DiI-oxLDL after intravenous injection for both spleen and liver. Whole-body dynamic planar images were acquired 10 min post injection of ¹²³I-oxLDL to generate regional time-activity curves (TACs) of the liver, heart, lungs, kidney, head, and abdomen. Regional radioactivity for those excised tissues as well as the bladder, stomach, gut, and thyroid were assessed using a gamma counter, yielding percent injected dose (%ID) and dose uptake ratio (DUR). The presence of ¹²³I-oxLDL in serum was assessed by radio-HPLC.@*RESULTS@#The cellular uptakes of ¹²³I-oxLDL were identical to those of DiI-oxLDL, and autoradiograms and fluorescence images also exhibited consistent distributions. TACs after injection of ¹²³I-oxLDL demonstrated extremely fast kinetics. The radioactivity uptake at 10 min postinjection was highest in the liver (40.8 ± 2.4% ID). Notably, radioactivity uptake was equivalent throughout the rest of the body (39.4 ± 2.7% ID). HPLC analysis revealed no remaining ¹²³I-oxLDL or its metabolites in the blood.@*CONCLUSION@#¹²³I-OxLDL was widely distributed not only in the liver, but also throughout the whole body, providing insight into the pathophysiological effects of oxLDL.