Radioiodinated cholesteryl ester analogs as residualizing tracers of lipoproteins disposition

Thesis/Dissertation · Sun Jan 01 04:00:00 EST 1989

OSTI ID:6321891

DeForge, L E

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
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMAL CELLS
ANIMALS
ARTERIOSCLEROSIS
BETA DECAY RADIOISOTOPES
BIOLOGICAL FUNCTIONS
BIOLOGICAL MODELS
BLOOD-PLASMA CLEARANCE
CARDIOVASCULAR DISEASES
CHEMICAL PREPARATION
CHOLESTEROL
CLEARANCE
CONNECTIVE TISSUE CELLS
COUNTING TECHNIQUES
DAYS LIVING RADIOISOTOPES
DIAGNOSIS
DIAGNOSTIC TECHNIQUES
DISEASES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ESTERS
FIBROBLASTS
FUNCTIONS
GUINEA PIGS
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
LIPIDS
LIPOPROTEINS
MAMMALS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PROTEINS
RABBITS
RADIOISOTOPE SCANNING
RADIOISOTOPES
RADIOPHARMACEUTICALS
RODENTS
SCINTISCANNING
SOMATIC CELLS
STEROIDS
STEROLS
SYNTHESIS
TRACER TECHNIQUES
VASCULAR DISEASES
VERTEBRATES