99mTc-galactosylated neoglycoalbumin (99mTc-NGA) is a hepatocyte-specific tracer that, after injection into the blood stream, delivers radioactivity selectively to the liver. This is based upon chemical recognition and binding by the
hepatic binding protein (HBP), a receptor specific for galactosylated
glycoproteins. Liver tissue samples were obtained intraoperatively from patients undergoing surgery for various
cancers. The concentration of specific
HBP receptors in the liver (normal liver,
hepatoma, liver
metastasis) was calculated from the in vitro binding of
99mTc-NGA. One week after surgery, the in vivo HBP density was also measured in some of these patients after injection of 3.5 mg (50 nmol per patient)
99mTc-NGA (150-200 MBq) for simulation of
99mTc-NGA kinetics. Comparison of in vitro and in vivo HBP concentration in the liver showed values in the same concentration range. In patients with
hepatoma or liver
metastasis a significantly (P less than 0.01) decreased global HBP density was found in vivo compared to controls. The values obtained for in vivo HBP concentration in the liver amounted to 0.38 +/- 0.05 mumol l-1 liver for patients with
hepatoma, to 0.4 +/- 0.1 mumol l-1 in patients with liver
metastasis and to 94 +/- 0.05 mumol l-1 liver in
cancer patients without liver
malignancy. In vitro investigation of HBP density revealed the malignant liver tissue to have a significantly (P less than 0.0001) decreased or almost (completely) absent
HBP receptor density compared to the normal tissue apart from the
cancer area. It is concluded that determination of HBP density in vivo via a specific tracer is a new, simple and reliable approach for the determination of remaining hepatic function in patients with primary or secondary
liver cancer.