Assessment of anti-atherogenic drugs in vivo and reconstitution of lipoproteins using radioiodinated cholesteryl iopanoate
A nonhydrolyzable radioiodinated cholesteryl ester, 125I-cholesteryl iopanoate (125I-Cl), was found to accumulate in high concentrations in atherosclerotic aortas of cholesterol-fed rabbits after intravenous administration. Aortas from normal chow-fed rabbits did not exhibit significant 125I-Cl accumulation. When cholesterol-fed rabbits were intravenously administered Tween-solubilized 125I-Cl and simultaneously treated with either of two anti-atherogenic compounds, estradiol 17..beta..-cypionate or colestipol, the extent of aortic atherosclerosis was found to dramatically decrease. Measurement of aortic radioactivity was found to strongly correlate with the severity of atherosclerosis. Although the specificity of 125I-Cl for atheromatous lesions was very good, gamma-camera scintigraphy of the abdomens of these rabbits 6 days after cessation of 125I-Cl administration was not able to consistently predict the severity of atherosclerosis. Tissue distribution studies suggested that high blood and spinal column bone marrow radioactivity produced aorta:nontarget radioactivity ratios unfavorable with respect to imaging. To improve this ratio so as to permit noninvasive imaging, attempts were made to incorporate 125I-Cl into serum lipoproteins. Labelling of either rabbit LDL by in vivo incorporation or human LDL by transfer of 125I-Cl from liposomes using cholesteryl ester transfer protein resulted in lipoproteins with low specific activity. Higher specific activity was achieved by reconstituting delipidated human LDL with a mixture of 125I-Cl and unlabeled cholesteryl oleate. These particles were taken up in high amounts by monolayers of human fibroblasts but not by fibroblasts deficient in LDL receptors or by normal fibroblasts during competition with unlabeled native LDL.
- Research Organization:
- Michigan Univ., Ann Arbor (USA)
- OSTI ID:
- 6859703
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ARTERIOSCLEROSIS
DIAGNOSIS
LIPOPROTEINS
BIOCHEMICAL REACTION KINETICS
AORTA
BIOLOGICAL ACCUMULATION
BLOOD
BLOOD SERUM
BONE MARROW
CHOLESTEROL
CHROMATOGRAPHY
DIET
DRUGS
ELECTROPHORESIS
FIBROBLASTS
IN VIVO
INTRAVENOUS INJECTION
IODINE 125
LABELLED COMPOUNDS
LIPOSOMES
RABBITS
RECEPTORS
RESPONSE MODIFYING FACTORS
SCINTISCANNING
TISSUE DISTRIBUTION
TRACER TECHNIQUES
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
ARTERIES
BETA DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BLOOD VESSELS
BODY
BODY FLUIDS
CARDIOVASCULAR DISEASES
CARDIOVASCULAR SYSTEM
CELL CONSTITUENTS
CONNECTIVE TISSUE CELLS
COUNTING TECHNIQUES
DAYS LIVING RADIOISOTOPES
DIAGNOSTIC TECHNIQUES
DISEASES
DISTRIBUTION
ELECTRON CAPTURE RADIOISOTOPES
HEMATOPOIETIC SYSTEM
HYDROXY COMPOUNDS
INJECTION
INTAKE
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIPIDS
MAMMALS
MATERIALS
MEMBRANE PROTEINS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANOIDS
ORGANS
PROTEINS
RADIOISOTOPE SCANNING
RADIOISOTOPES
REACTION KINETICS
SEPARATION PROCESSES
SOMATIC CELLS
STEROIDS
STEROLS
TISSUES
VASCULAR DISEASES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques