Radioiodinated cholesteryl ester analogs as residualizing tracers of lipoproteins disposition
Due to the importance of low density lipoprotein (LDL) in lipid metabolism and atherosclerosis, efforts were made to incorporate {sup 125}I-cholesteryl iopanoate ({sup 125}I-CI), a residualizing cholesteryl ester (CE) analog, into the lipid core of LDL. This preparation is potentially useful as a scintigraphically detectable tracer of LDL uptake into atheroma and tissues such as the adrenal and liver. Initial studies using a cholesterol-fed rabbit model of atherosclerosis validated the use of {sup 125}I-CI as a tracer of CE deposition. However, scintigraphy revealed considerable nonspecific {sup 125}I-CI uptake due to tissue cholesterol loading. An alternative animal model was the guinea pig, which responds moderately to cholesterol feeding and carries the plasma cholesterol predominantly as LDL. Dietary fat and cholesterol, coupled with chronic aortic injury caused by an indwelling catheter, resulted in lipid containing, smooth muscle cell proliferative lesions in many animals. However, further studies are necessary to fully characterize this model. In additional studies, in vitro methods for incorporating {sup 125}I-CI into LDL were examined. These included a reconstitution procedure described by Krieger et al. and a procedure involving incubation of detergent (Tween 20)-solubilized {sup 125}I-CI with plasma. Although both LDL preparations were taken up normally by cultured fibroblasts, the plasma clearance rate of reconstituted LDL was markedly abnormal in guinea pigs. In contrast, LDL labeled by the detergent method cleared from the plasma identically to a radioiodinated LDL control. Therefore, this latter procedure was also used to incorporate two novel radioiodinated cholesteryl ether analogs {sup 125}I-CI cholesteryl m-iodobenzyl ether ({sup 125}I-CIDE) and {sup 125}I-cholesteryl 12-(miodophenyl)dodecyl ether ({sup 125}I-CIDE) into LDL.
- Research Organization:
- Michigan Univ., Ann Arbor, MI (USA)
- OSTI ID:
- 6321891
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ARTERIOSCLEROSIS
DIAGNOSIS
LIPOPROTEINS
BIOLOGICAL FUNCTIONS
RADIOPHARMACEUTICALS
CHEMICAL PREPARATION
BIOLOGICAL MODELS
BLOOD-PLASMA CLEARANCE
CHOLESTEROL
ESTERS
FIBROBLASTS
GUINEA PIGS
IODINE 125
RABBITS
SCINTISCANNING
TRACER TECHNIQUES
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
CARDIOVASCULAR DISEASES
CLEARANCE
CONNECTIVE TISSUE CELLS
COUNTING TECHNIQUES
DAYS LIVING RADIOISOTOPES
DIAGNOSTIC TECHNIQUES
DISEASES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
FUNCTIONS
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
LIPIDS
MAMMALS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PROTEINS
RADIOISOTOPE SCANNING
RADIOISOTOPES
RODENTS
SOMATIC CELLS
STEROIDS
STEROLS
SYNTHESIS
VASCULAR DISEASES
VERTEBRATES
550601* - Medicine- Unsealed Radionuclides in Diagnostics