ABSTRACT
Two different methods were evaluated for incorporating [125I]cholesteryl iopanoate ([125I]CI), a non-hydrolyzable cholesteryl ester analog, into LDL. The first procedure was an organic solvent delipidation-reconstitution procedure (R[125I-CI]LDL) while the second involved incubation of detergent (Tween-20)-solubilized [125I]CI with whole plasma (D[125I-CI]LDL). R[125I-CI]LDL behaved similar to native LDL in vitro, but was markedly different in vivo, apparently due to a heterogeneity in particle size. D[125I-CI]LDL, however, was metabolized normally both in vitro and in vivo. These results, combined with the residualizing nature of [125I]CI, demonstrate that D[125I-CI]LDL is appropriate for tracing LDL uptake in vivo.
Subject(s)
Cholesterol Esters/pharmacokinetics , Iodine Radioisotopes/metabolism , Lipoproteins, LDL/metabolism , Adrenal Glands/metabolism , Animals , Fibroblasts/metabolism , Guinea Pigs , Humans , Iodine Radioisotopes/pharmacokinetics , Lipoproteins, LDL/pharmacokinetics , Liver/metabolism , Male , Metabolic Clearance Rate , Thyroid Gland/metabolism , Tissue DistributionSubject(s)
Drug Delivery Systems/methods , Lipoproteins/administration & dosage , Pharmaceutical Preparations/administration & dosage , Radioisotopes/administration & dosage , Radionuclide Imaging/methods , Adrenal Glands/diagnostic imaging , Arteriosclerosis/diagnostic imaging , Drug Carriers/administration & dosage , Female , Humans , Lipoproteins/chemistry , Liver/diagnostic imaging , Neoplasms/diagnostic imaging , Ovary/diagnostic imagingABSTRACT
In an effort to visualize whole body cholesteryl ester (CE) deposition using the nuclear medicine imaging technique of gamma camera scintigraphy, 125I-cholesteryl iopanoate (125I-CI), a nonhydrolyzable CE analogue, was used as a marker for CE deposition in atherosclerotic New Zealand white rabbits. Groups of animals were fed either a cholesterol-enriched diet (2%, w/w) or the same diet supplemented with the hypolipidemic drugs colestipol (1%, w/w) and/or clofibrate (0.3%, w/w). Injections of 125I-CI were administered biweekly. At the end of 15 weeks, animals were scintigraphically scanned and sacrificed for tissue analysis. The results demonstrated that while drug treatment had no significant effect on plasma lipid levels, it substantially lessened atherosclerotic involvement in the thoracic-abdominal aorta. These differences in aortic lipid accumulation were reflected in the whole-body scans which showed a reduction in tissue accumulation of 125I-CI in the drug-treated groups. Gamma camera scintigraphy thus represents a rapid means of visualizing tissue CE accumulation which could facilitate the evaluation of lipid-lowering drug efficacy and possible antiatherosclerotic effect.
Subject(s)
Arteriosclerosis/drug therapy , Cholesterol Esters/metabolism , Clofibrate/therapeutic use , Colestipol/therapeutic use , Polyamines/therapeutic use , Animals , Arteriosclerosis/etiology , Arteriosclerosis/metabolism , Cholesterol, Dietary , Female , Iodine Radioisotopes , Rabbits , Radionuclide ImagingABSTRACT
Rabbits rendered atherosclerotic by mechanical aortic de-endothelialization and 6 wk of cholesterol feeding were administered estradiol-17 beta-cypionate, an anti-atherogenic agent in rabbits. These animals were compared to a similar, untreated group and control animals fed a regular non-atherogenic diet. Iodine-125 cholesteryl iopanoate ([125I]Cl), a nonhydrolyzable cholesteryl ester derivative, was administered intravenously at regular intervals throughout the study. Six days after the last dose of [125I]Cl, the animals were scanned with a gamma camera. After animals were killed, tissue distribution of the 125I radioactivity showed a significant decrease of [125I]CI accumulation in the aorta of estrogen-treated as compared to untreated, cholesterol-fed animals. However, the accumulation of [125I]CI in the aortas was insufficient to accurately define the presence of atheroma by gamma camera scintigraphy.
