The overall goal of this proposal is to develop and validate a method for imaging lipoprotein distribution in various organs and in atheroma. This will be accomplished with the use of a class of radiopharmaceuticals new to nuclear medicine - radiolabelled lipoproteins. Studies in our laboratory have shown that the healing wall of the experimentally injured aorta of the rabbit selectively accumulates low-density lipoproteins (LDL) and that this vessel can be imaged extracorporeally with radiolabelled low-density lipoproteins (LDL). The uptake of LDL by multiple organs can also be estimated. Our published preliminary studies in man with 125I radiolabelled LDL have shown that carotid atheroma can also be imaged extracorporeally. We propose to extend these studies to various modified lipoproteins and to more appropriate radiolabels such as 99mTc.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Metabolism Study Section (MET)
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Beth Israel Deaconess Medical Center
United States
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Chang, M Y; Lees, A M; Lees, R S (1993) Low-density lipoprotein modification and arterial wall accumulation in a rabbit model of atherosclerosis. Biochemistry 32:8518-24
Taylor, J W; Shih, I L; Lees, A M et al. (1993) Surface-induced conformational switching in amphiphilic peptide segments of apolipoproteins B and E and model peptides. Int J Pept Protein Res 41:536-47
Chang, M Y; Lees, A M; Lees, R S (1992) Time course of 125I-labeled LDL accumulation in the healing, balloon-deendothelialized rabbit aorta. Arterioscler Thromb 12:1088-98
Lees, A M; Lees, R S (1991) 99mTechnetium-labeled low density lipoprotein: receptor recognition and intracellular sequestration of radiolabel. J Lipid Res 32:1-8
Shih, I L; Lees, R S; Chang, M Y et al. (1990) Focal accumulation of an apolipoprotein B-based synthetic oligopeptide in the healing rabbit arterial wall. Proc Natl Acad Sci U S A 87:1436-40
Lees, A M; Lees, R S; Schoen, F J et al. (1988) Imaging human atherosclerosis with 99mTc-labeled low density lipoproteins. Arteriosclerosis 8:461-70
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Fischman, A J; Lees, A M; Lees, R S et al. (1987) Accumulation of native and methylated low density lipoproteins by healing rabbit arterial wall. Arteriosclerosis 7:361-6
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