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Measurement of Receptor Concentration and Forward-Binding Rate Constant Via Radiopharmacokinetic Modeling of Technetium-99m-Galactosyl-Neoglycoalbumin

Departments of Radiology and Internal Medicine, University of California, Davis, Medical Center, Sacramento, California

Correspondence: For reprints contact: David R. Vera, PhD, Division of Nuclear Medicine, University of California, Davis, Medical Center, 2315 Stockton Blvd., Sacramento, CA 95817.

ABSTRACT

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.

FOOTNOTES

^* Current address: Department of Radiology, University of Washington Medical Center, Seattle, WA.

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