Measurement of receptor concentration and forward-binding rate constant via radiopharmacokinetic modeling of technetium-99m-galactosyl-neoglycoalbumin

Technetium-99m-galactosyl-neoglycoalbumin (^99mTc-NGA) is a synthetic ligand to the hepatocyte receptor, hepatic binding protein (HBP). A five-state mathematical model containing a bimolecular chemical reaction was utilized for quantitative estimation of the following physiologic and biochemical parameters: extrahepatic plasma volume V(e); hepatic plasma flow F and volume V(h); receptor-ligand forward-binding rate constant k(b) and reaction volume V(r); and receptor concentration [R](o). Nine normal subjects were studied. Given (a) liver and heart time-activity data, (b) the patient's weight, height, and hematocrit, (c) the fraction of injected dose in a 3-min blood sample, and (d) the amount and galactose density of the NGA dose, a computer program executed a curve-fit to the kinetic model. Systematic error, as measured by reduced chi-square, ranged from 1.43 to 2.56. Based on the nine imaging studies, the mean and relative error of each parameter were: [R](o), 0.813 ± (0.11) μM; k(b), 2.25 ± (0.15) μM^-1 min^-1; F, 0.896 ± (0.20) liter/min; V(e), 1.67 ± (0.27) liter; and V(h), 0.228 ± (0.22) liter. Two unique features of ^99mTc-NGA radiopharmacokinetic systems permit the simultaneous estimates of receptor quantity, ligand affinity, and hepatic plasma flow. The first is the ability to administer a quantity of ligand capable of occupying a significant fraction of receptor; and the second is a simple model structure that conserves mass.