TY - JOUR
T1 - Tc-99m galactosyl-neoglycoalbumin
T2 - In vitro characterization of receptor-mediated binding
AU - Vera, D. R.
AU - Krohn, K. A.
AU - Stadalnik, R. C.
AU - Scheibe, P. O.
PY - 1984
Y1 - 1984
N2 - Hepatic binding protein (HBP) is a membrane receptor that binds and transports plasma glycoproteins from hepatic blood to hepatocellular lysosomes. We have characterized the in vitro binding of Tc-99m galactosyl-neoglycoalbumin (Tc-NGA), a synthetic HBP ligand, to liver membrane. Structural modifications of NGA resulted in the alteration of the equilibrium constant, K(A), and the forward-binding rate constant, k(b). Binding was second-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, asialo-orosomucoid. We used computer simulation to study the detectability of the changes in HBP concentration at different values of k(b). 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 to 25 galactose units per albumin molecule.
AB - Hepatic binding protein (HBP) is a membrane receptor that binds and transports plasma glycoproteins from hepatic blood to hepatocellular lysosomes. We have characterized the in vitro binding of Tc-99m galactosyl-neoglycoalbumin (Tc-NGA), a synthetic HBP ligand, to liver membrane. Structural modifications of NGA resulted in the alteration of the equilibrium constant, K(A), and the forward-binding rate constant, k(b). Binding was second-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, asialo-orosomucoid. We used computer simulation to study the detectability of the changes in HBP concentration at different values of k(b). 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 to 25 galactose units per albumin molecule.
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M3 - Article
C2 - 6737077
AN - SCOPUS:0021245955
SN - 0161-5505
VL - 25
SP - 779
EP - 787
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 7
ER -