Atushi Nakano1,2, Hidekazu Kawashima1,3, Yoshinori Miyake1, Tsutomu Zeniya1,4, Akihide Yamamoto1, Kazuhiro Koshino1, Takashi Temma1,5, Tetsuya Fukuda6, Yoshiko Fujita7, Akemi Kakino7, Shigehiko Kanaya8, Tatsuya Sawamura7, Hidehiro Iida1,6,8. 1. 1Department of Investigative Radiology, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565 Japan. 2. 2Department of Vascular Physiology, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka, Japan. 3. 3Radioisotope Research Center, Kyoto Pharmaceutical University, 1 Misasagi-shichono-cho, Yamashina-ku, Kyoto, Japan. 4. 4Graduate School of Science and Technology, Hirosaki University, Bunkyo-cho, Hirosaki, Aomori, Japan. 5. 5Department of Biofunctional Analysis, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka, Japan. 6. Department Radiology, National Cerebral and Cardiovacular Center, 5-7-1 Fujishiro-dai, Suita, Osaka, Japan. 7. 7Department of Physiology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, Japan. 8. Computational Systems Biology Laboratory, Graduate School of Information Science, Nara Institute of Science and Techonology, Takayama, Nara, Japan.
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 post-injection 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.
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 post-injection 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.
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