99mTc-low density lipoprotein: intracellularly trapped radiotracer for noninvasive imaging of low density lipoprotein metabolism in vivo.
Low density lipoprotein (LDL) is the major transport protein for endogenous cholesterol in human plasma. LDL can be radiolabeled with 99mTc using sodium dithionite as a reducing agent. Biodistribution studies of 99mTc-LDL in normal rabbits confirm that 99mTc-LDL acts as an intracellularly "trapped ligand" similar to radioiodinated tyramine cellobiose-LDL (the previously validated trapped radioligand). In addition, studies performed in hypercholesterolemic rabbit models demonstrated the feasibility of imaging hepatic LDL-receptor concentration noninvasively. 99mTc-LDL imaging studies in a number of hypercholesterolemic and hypocholesterolemic patients have proven useful in understanding the abnormal uptake and metabolism of LDL. In patients with hypercholesterolemia (HC), 99mTc-LDL appears to be taken up well by the actively evolving atherosclerotic lesions and xanthomata that contained foam cells and macrophages. In patients with myeloproliferative disease and chronic hypocholesterolemia, 99mTc-LDL images showed intense accumulation of radioactivity in the spleen and bone marrow; this demonstrated extensive proliferation of the macrophage population suggesting that hypocholesterolemia in these patients may be due to increased uptake of LDL uptake by the macrophages. 99mTc-LDL is a powerful tool for the noninvasive exploration of a variety of disorders of lipoprotein metabolism in patients.
Department of Physics-Nuclear Medicine, Mount Sinai Medical Center, New York, NY 10029.
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Vallabhajosula
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Goldsmith
D000818:Animals; D001161:Arteriosclerosis / Q000000981:diagnostic imaging; D006801:Humans; D006937:Hypercholesterolemia / Q000000981:diagnostic imaging; D008077:Lipoproteins, LDL; D009196:Myeloproliferative Disorders / Q000000981:diagnostic imaging; D015609:Organotechnetium Compounds; D011817:Rabbits; D011877:Radionuclide Imaging; D014973:Xanthomatosis / Q000000981:diagnostic imaging
D008077:Lipoproteins, LDL; D015609:Organotechnetium Compounds; C058312:technetium Tc 99m low-density lipoprotein