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Radiolabeled Cholesteryl lopanoate/ Acetylated Low Density Lipoprotein as a Potential Probe for Visualization of Early Atherosclerotic Lesions in Rabbits

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Abstract

Purpose. Atherosclerosis is the underlying factor leading to such cardiovascular diseases (CVD) as stroke, aneurysm, and myocardial infarction. The early detection of atherosclerotic plaques is considered to be crucial for successful prevention and/or therapeutic and dietary intervention of CVD. Current diagnostic practice, on the other hand, can only detect the problem at an advanced stage. The purpose of this study was to examine the potential of using a radiolabeled cholesterol ester analog/acetylated low density lipoprotein (AcLDL) conjugate as a diagnostic agent for the early and non-invasive detection of atherosclerosis and for the monitoring of the effects of drug therapy.

Methods. Cholesteryl iopanoate (CI), a cholesterylester analog, was synthesized, radiolabeled, and incorporated into AcLDL. Early atherosclerotic lesions were induced in New Zealand White rabbits. 125I-C1/ AcLDL was injected intravenously at 2 μCi/kg. Blood samples were taken at different time intervals after injection and clearance of the injected drug from blood was studied. The rabbits were sacrificed after 72 hours and the distribution of radioactivity in various organs was investigated. Aortae of both atherosclerotic lesion and control rabbits were removed for Sudan IV staining and autoradiography in order to confirm the formation of the atherosclerotic lesion and localization of radioactivity.

Results. The injected drug was found to be cleared from blood following a two compartment model. Radioactivity in the atherosclerotic aorta was found to be about 8 times higher than that in normal aorta, suggesting that the proposed diagnostic probe was selectively taken up by the atherosclerotic lesion. The autoradiography and staining confirmed that the localization of the proposed probe was superimposed with the atherosclerotic lesion site.

Conclusions. The results suggested that incorporation of CI into AcLDL resulted in the selective localization of CI at the atherosclerotic plaque areas. CI/AcLDL labeled with appropriate radioisotope has the potential to be used as a probe for visualization of early atherosclerotic lesion using scintigraphy technology.

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Authors and Affiliations

  1. School of Pharmacy, Memorial University of Newfoundland, St. John's, New Foundland, A1B 3V6, Canada

    W. Xiao, L. Wang & H. Liu

  2. Division of Basic Medical Science, Faculty of Medicine, Memorial University of Newfoundland, St. John's, New Foundland, A1B 3V6, Canada

    T. Scott & H. Liu

  3. Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan, 48109

    R. E. Counsell

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  1. W. Xiao
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  2. L. Wang
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  3. T. Scott
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  4. R. E. Counsell
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  5. H. Liu
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Correspondence to H. Liu.

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Xiao, W., Wang, L., Scott, T. et al. Radiolabeled Cholesteryl lopanoate/ Acetylated Low Density Lipoprotein as a Potential Probe for Visualization of Early Atherosclerotic Lesions in Rabbits. Pharm Res 16, 420–426 (1999). https://doi.org/10.1023/A:1018881904228

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