Functional liver imaging with 99 Tcm-galactosyl-neoglycoalbumin (NGA) in alcoholic liver cirrhosis and liver fibrosis

Abstract

Synthesis of 99Tcm-galactosyl-neoglycoalbumin (99Tcm-NGA), a recently described new radioligand with high specificity for hepatic binding protein (HBP), a galactose-residue specific receptor on hepatocytes, was carried out by covalent coupling of 2-imino-2-methoxyethyl-1-thio-beta-D-galactopyranoside to the primary amino groups of human serum albumin. NGA was purified by ultrafiltration and size exclusion high-pressure liquid chromatography (HPLC). Using a computer-based simulation program, time-activity data for the liver and precordium, blood radioactivity 2 min after i.v. injection of the radioligand, the association constant of 99Tcm-NGA-binding to HBP measured on human liver biopsies in vitro, and other patient-related parameters were put into a five-state non-linear model describing the pharmacokinetics of 99Tcm-NGA. By fitting the parameters of the model iteratively to the experimental data, an estimate of HBP concentration in the liver and of total liver blood flow was obtained. Using this model we studied 32 patients (53 +/- 11 years) with different clinical stages of alcoholic liver cirrhosis. Child B and Child C stage cirrhotic patients had a lower HBP concentration in the liver compared to control individuals (0.96 +/- 0.21 mumol l-1). The group with the most advanced cirrhosis (Child C stage) had a significantly lower HBP concentration (0.27 +/- 0.15 mumol l-1) than Child A patients (0.66 +/- 0.21 mumol l-1; P less than 0.01) and Child B patients (0.53 +/- 0.18 mumol l-1; P less than 0.05). In four patients with biopsy-proven liver fibrosis (0.84 +/- 0.20 mumol l-1) no difference in receptor concentration from normal individuals was estimated. Changes in liver blood flow were not significant between the groups. A direct comparison of HBP concentration estimated in vivo by 99Tcm-NGA functional imaging and HBP concentration measured in vitro on a surgically removed liver biopsy specimen from the same patient with a normal liver and liver cirrhosis showed good matching of these two values. The results suggest that in vivo estimation of HBP concentration in the liver by 99Tcm-NGA functional imaging might be a suitable method for determining liver cell mass.