QUANTIFICATION OF HUMAN HEPATIC BINDING-PROTEIN (HBP) VIA TC-99M-GALACTOSYL-NEOGLYCOALBUMIN (NGA) LIVER SCINTIGRAPHY

Tc-99m-galactosyl-neoglycoalbumin (Tc-99m-NGA) was synthesized by covalent coupling of 2-imino-2-methoxyethyl-1-thio-beta-D-galactopyranoside to the primary amino groups of human serum albumin. Injection of Tc-99m-NGA (150 MBq; 3.5 mg (= 50 nmol)/ml demonstrated the liver to be the exclusive site of tracer-uptake. Simulation of Tc-99m-NGA-kinetics allowed quantification of binding to the hepatic binding protein (HBP). Using this model we studied 250 patients with various liver disease. In alcoholic liver cirrhosis such patients with Child B and Child C stage cirrhosis had a lower HBP-concentration in the liver compared to control individuals (0.85-1.2-mu-mol/l). The group with the most advanced cirrhosis (Child C stage) had a significantly lower HBP-concentration (0.20-0.45-mu-mol/l) than Child A patients (0.60-0.85-mu-mol/l; p < 0.01) and Child B patients (0,45-0.60-mu-mol/l; p < 0.05). In patients with biopsy proven liver fibrosis (0.80-1.22-mu-mol/l) no difference in receptor concentration to normal individuals was estimated. Patients with recently diagnosed acute viral hepatitis underwent repeated Tc-99m-galactosyl-neoglycoalbumin (NGA) scanning of the liver during the course of the disease. Return of liver function tests to normal values was associated with an increased hepatic imaging size as well as increase in HBP-concentration (up to a 3-fold of initial concentration). In patients exhibiting a prolonged course of the disease changes in NGA-kinetic data were borderline and the hepatic image size unchanged. The values obtained for HBP-concentration in the liver amounted to 0.30-0.50-mu-mol/l liver for patients with hepatoma, to 0.40-0.60-mu-mol/l in patients with liver metastasis and to 0.90-1.20-mu-mol/l in cancer patients without liver malignancy. It is concluded that scintigraphic evaluation of functional hepatic cell mass using the new receptor-tracer Tc-99m-NGA provides an in vivo diagnostic mean allowing quantitative data on liver function beside assessment of liver morphology.