Nucl Med Mol Imaging.  2018 Apr;52(2):144-153. 10.1007/s13139-017-0497-2.

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

Affiliations
  • 1Department of Investigative Radiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan. iida@ri.ncvc.go.jp
  • 2Department of Vascular Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan.
  • 3Radioisotope Research Center, Kyoto Pharmaceutical University, Kyoto, Japan.
  • 4Graduate School of Science and Technology, Hirosaki University, Hirosaki, Aomori, Japan.
  • 5Department of Biofunctional Analysis, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.
  • 6Department Radiology, National Cerebral and Cardiovacular Center, Suita, Osaka, Japan.
  • 7Department of Physiology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
  • 8Computational 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 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.

Keyword

Oxidized low-density lipoprotein (oxLDL); Radiolabeled ligand; Dynamic planar imaging; Biodistribution

MeSH Terms

Abdomen
Animals
Atherosclerosis
CHO Cells
Chromatography, High Pressure Liquid
Cricetinae
Fluorescence
Head Kidney
Heart
Inflammation
Injections, Intravenous
Iodine
Kinetics
Lipoproteins
Liver
Lung
Methods
Mice*
Radioactivity
Spleen
Stomach
Thyroid Gland
Urinary Bladder
Iodine
Lipoproteins
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