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Ex Vivo Evaluation of a Novel Polyiodinated Compound for Early Detection of Atherosclerosis

Zhili Kang, Thomas M. Scott, Carl Wesolowski, Liping Feng, Jinguo Wang, Lili Wang and Hu Liu
Radiation Research
Vol. 160, No. 4 (Oct., 2003), pp. 460-466
Stable URL: http://www.jstor.org/stable/3581221
Page Count: 7
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Ex Vivo Evaluation of a Novel Polyiodinated Compound for Early Detection of Atherosclerosis
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Abstract

Atherosclerosis is a primary cause of heart disease and stroke; it is the underlying cause of about 50% of all deaths in Western countries. It is known that early detection of atherosclerotic lesions would significantly reduce the risk of mortality. The objective of this study was to develop a radioimaging method for early detection of atherosclerotic plaques. A novel polyiodinated cholesterol analog, cholesteryl 1,3-diiopanoate glyceryl ether (C2I, patent pending), was synthesized and radiolabeled with 125 I. ${}^{125}{\rm I}\text{-}{\rm C}2{\rm I}$ was incorporated into acetylated low-density lipoprotein (AcLDL), which is considered to be an atherosclerotic plaque-seeking carrier. ${}^{125}{\rm I}\text{-}{\rm C}2{\rm I}$ was also prepared as a chylomicron-like emulsion. Transgenic mice deficient in apoE and low-density lipoprotein receptors (LDLR), known as apoE/LDLR double knockout, were used as an animal model of early atherosclerosis. ${}^{125}{\rm I}\text{-}{\rm C}2{\rm I}/{\rm AcLDL}$ or ${}^{125}{\rm I}\text{-}{\rm C}2{\rm I}$ emulsion was injected into the apoE/LDLR knockout mice via the tail vein, and the mice were killed humanely 24 h after injection. Various tissues including aorta were removed and radioactivity was determined. The aorta samples were also imaged to determine the accumulation of radioactivity from C2I. The images were compared to the atherosclerotic lesions revealed by histological studies. It was found that both ${}^{125}{\rm I}\text{-}{\rm C}2{\rm I}/{\rm AcLDL}$ and ${}^{125}{\rm I}\text{-}{\rm C}2{\rm I}$ emulsion resulted in accumulation of radioactivity at the site of early atherosclerotic lesions, and they therefore may be useful for early detection of atherosclerosis.

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