Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL032975-03
Application #
3344552
Study Section
Metabolism Study Section (MET)
Project Start
1984-07-01
Project End
1989-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02215

  Publications

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
Miller, A; Schoen, F J; Lees, A M et al. (1987) Low density lipoprotein accumulation by PTFE grafts in the rabbit aorta. Autoradiographic-morphologic correlations. ASAIO Trans 33:489-93
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
Isaacsohn, J L; Lees, A M; Lees, R S et al. (1986) Adrenal imaging with technetium-99m-labelled low density lipoproteins. Metabolism 35:364-6
Lees, R S; Garabedian, H D; Lees, A M et al. (1985) Technetium-99m low density lipoproteins: preparation and biodistribution. J Nucl Med 26:1056-62