TC-99M GALACTOSYL-NEOGLYCOALBUMIN - INVITRO CHARACTERIZATION OF RECEPTOR-MEDIATED BINDING

  • 1 January 1984
    • journal article
    • research article
    • Vol. 25  (7) , 779-787
Abstract
Hepatic binding protein (HBP) is a membrane receptor that binds and transports plasma glycoproteins from hepatic blood to hepatocellular lysosomes. The in vitro binding of 99mTc galactosyl-neoglycoalbumin (Tc-NGA), a synthetic HBP ligand, to rabbit liver membrane was characterized. Structural modifications of NGA resulted in the alteration of the equilibrium constant, KA and the forward-binding rate constant, kb. Binding was 2nd-order; the relative amount of membrane-bound NGA depended on the initial concentrations of ligand and membrane. Membrane displacement studies, using carrier ligands in contrast to previously bound Tc-NGA or I-NGA, correlated with the binding characteristics of a native HBP ligand, asialoorosomucoid. Computer simulation was used to study the detectability of the changes in HBP concentration at different values of kb. The simulations indicated that radiopharmacokinetic sensitivity to alterations in [HBP] should be possible using a neoglycoalbumin preparation with a carbohydrate density within the range of 15-25 galactose units per albumin molecule.