title: Indium-111-labeled LDL: a potential agent for imaging atherosclerotic disease and lipoprotein biodistribution.
abstract: Radiolabeling of low-density lipoprotein (LDL) and external imaging with a gamma camera would offer a means of taking advantage of the metabolic activity of developing atherosclerotic lesions in order to noninvasively detect and determine the extent of atherosclerotic cardiovascular disease. Indium-111-(111In) labeled LDL was prepared and its purity demonstrated by agarose electrophoresis and ultracentrifugation. In vitro studies with cultured human fibroblasts demonstrated significant inhibition of iodine-125-(125I) LDL binding to LDL receptors by 111In-LDL, although this was less than the inhibition produced by unlabeled LDL. Adrenal gland uptake of 111In-LDL by hypercholesterolemic rabbits was reduced by 86% compared to the level of uptake observed in normal rabbits. These results were compatible with downregulation of adrenal LDL receptors in the hypercholesterolemic rabbits. Uptake of 111In-LDL in the atherosclerotic proximal aorta of hypercholesterolemic rabbits was 2.5 times higher than in normal rabbits. These results suggest that 111In-LDL has the potential to be a useful agent for external imaging of atherosclerotic lesions and lipoprotein biodistribution.
authors.affiliation: Department of Radiology (Nuclear Medicine), Columbia University College of Physicians and Surgeons, New York, New York 10032.
authors.forename: J M
authors.initials: JM
authors.lastname: Rosen
authors.forename: S P
authors.initials: SP
authors.lastname: Butler
authors.forename: G E
authors.initials: GE
authors.lastname: Meinken
authors.forename: T S
authors.initials: TS
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Ramakrishnan
authors.forename: S C
authors.initials: SC
authors.lastname: Srivastava
authors.forename: P O
authors.initials: PO
authors.lastname: Alderson
authors.forename: H N
authors.initials: HN
authors.lastname: Ginsberg
mesh_terms: D000818:Animals; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging*; D006801:Humans; D006937:Hypercholesterolemia / Q000000981:diagnostic imaging*; D007205:Indium Radioisotopes; D008077:Lipoproteins, LDL / Q000493:pharmacokinetics; D008297:Male; D004369:Pentetic Acid; D011817:Rabbits; D011877:Radionuclide Imaging; D011973:Receptors, LDL / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D007205:Indium Radioisotopes; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D004369:Pentetic Acid