123I–Labeled oxLDL Is Widely Distributed Throughout the Whole Body in Mice
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.
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.
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.
123I–OxLDL was widely distributed not only in the liver, but also throughout the whole body, providing insight into the pathophysiological effects of oxLDL.
KeywordsOxidized low-density lipoprotein (oxLDL) Radiolabeled ligand Dynamic planar imaging Biodistribution
The authors would like to thank Dr. Kyoko Shioya, DVM from Laboratory of Animal Experiment and Medicine Management, National Cerebral and Cardiovascular Center, Osaka, Japan, for her assistance and advise on animal care and experimental procedures.
Compliance with Ethical Standards
Conflict of Interest
Atushi Nakano, Hidekazu Kawashima, Yoshinori Miyake, Tsutomu Zeniya, Kazuhiro Koshino, Takashi Temma, Tetsuya Fukuda, Yoshiko Fujita, Akemi Kakino, Shigehiko Kanaya, and Tatsuya Sawamura declare that they have no conflict of interest. Hidehiro Iida received research grants from Chugai Yakuhin, Japan, Nihon Medi Physics, Japan and Molecular Imaging Labo, Japan. Akihide Yamamoto is paid by Molecular Imaging lab, Japan. This study was supported by the Budget for Nuclear Research of MEXT (Ministry of Education, Culture, Sports, Science and Technology Japan), a Grant for Translational Research from MHLW (Ministry of Health, Labor and Welfare, Japan), a Grant for Strategic Japanese-Finnish Research Cooperative Program on “Application of Medical ICT Devices” from Japan Agency for Medical Research and Development (AMED), Japan, and JSPS KAKENHI Grants (Number: 24,601,021 and 15 K01309).
The animal experiments in this study were conducted in accordance with guidelines for animal research on Human Care and Use of Laboratory Animals (Rockville, National Institute of Health/Office for Protection from Research Risks, 1996). The study protocol was approved by the Sub-committee for Laboratory Animal Welfare, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan.
The present study included only animal data, thus our institute approved that the requirement to obtain informed consent was waived.
- 26.R Core Team. R: A language and environment for statistical computing, version 3.2.2. R Foundation for Statistical Computing, Vienna, Austria; 2014. http://www.R-project.org/.
- 35.Luoto P, Laitinen I, Suilamo S, Nagren K, Roivainen A. Human dosimetry of carbon-11 labeled N-butan-2-yl-1-(2-chlorophenyl)-N-methylisoquinoline-3-carboxamide extrapolated from whole-body distribution kinetics and radiometabolism in rats. Mol Imaging Biol. 2010;12(4):435–42.CrossRefPubMedGoogle Scholar