Indium-111-labeled LDL: a potential agent for imaging atherosclerotic disease and lipoprotein biodistribution.
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.
Rosen
J M
JM
Department of Radiology (Nuclear Medicine), Columbia University College of Physicians and Surgeons, New York, New York 10032.
Butler
S P
SP
Meinken
G E
GE
Wang
T S
TS
Ramakrishnan
R
R
Srivastava
S C
SC
Alderson
P O
PO
Ginsberg
H N
HN
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
D007205:Indium Radioisotopes; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D004369:Pentetic Acid