(123)I-Labeled oxLDL Is Widely Distributed Throughout the Whole Body in Mice.

(123)I标记的oxLDL广泛分布于小鼠全身

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作者:Nakano Atushi, Kawashima Hidekazu, Miyake Yoshinori, Zeniya Tsutomu, Yamamoto Akihide, Koshino Kazuhiro, Temma Takashi, Fukuda Tetsuya, Fujita Yoshiko, Kakino Akemi, Kanaya Shigehiko, Sawamura Tatsuya, Iida Hidehiro
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 (123)I-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 (123)I-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 (123)I-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 (123)I-oxLDL in serum was assessed by radio-HPLC. RESULTS: The cellular uptakes of (123)I-oxLDL were identical to those of DiI-oxLDL, and autoradiograms and fluorescence images also exhibited consistent distributions. TACs after injection of (123)I-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 (123)I-oxLDL or its metabolites in the blood. CONCLUSION: (123)I-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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