A1 Refereed original research article in a scientific journal
I-123-Labeled oxLDL Is Widely Distributed Throughout the Whole Body in Mice
Authors: Nakano A, Kawashima H, Miyake Y, Zeniya T, Yamamoto A, Koshino K, Temma T, Fukuda T, Fujita Y, Kakino A, Kanaya S, Sawamura T, Iida H
Publisher: SPRINGER HEIDELBERG
Publication year: 2018
Journal: Nuclear Medicine and Molecular Imaging
Journal name in source: NUCLEAR MEDICINE AND MOLECULAR IMAGING
Journal acronym: NUCL MED MOLEC IMAG
Volume: 52
Issue: 2
First page : 144
Last page: 153
Number of pages: 10
ISSN: 1869-3474
DOI: https://doi.org/10.1007/s13139-017-0497-2
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 I-123-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 I-123-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 I-123-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 I-123-oxLDL in serum was assessed by radio-HPLC.Results The cellular uptakes of I-123-oxLDL were identical to those of DiI-oxLDL, and autoradiograms and fluorescence images also exhibited consistent distributions. TACs after injection of I-123-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 I-123-oxLDL or its metabolites in the blood.Conclusion I-123-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 I-123-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 I-123-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 I-123-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 I-123-oxLDL in serum was assessed by radio-HPLC.Results The cellular uptakes of I-123-oxLDL were identical to those of DiI-oxLDL, and autoradiograms and fluorescence images also exhibited consistent distributions. TACs after injection of I-123-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 I-123-oxLDL or its metabolites in the blood.Conclusion I-123-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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