Differential receptor targeting of liver cells using Tc-99m-neoglycosylated human serum albumins

Abstract

Neolactosyl human serum albumin (LSA) targets asialoglycoprotein receptor and shows high liver uptake due to accumulation in hepatocytes. Although neomannosyl human serum albumin (MSA) also shows high liver uptake, it has been reported to be taken up by Kupffer cells and endothelial cells. We compared the biological properties of LSA and MSA. Tc-99m-LSA and Tc-99m-MSA biodistribution in mice were investigated after intravenous injection. In vivo localization of rhodaminisothiocyanate (RITC)-LSA and fluoresceineisothiocyanate (FITC)-MSA were investigated in mouse liver. Excretion routes of Tc-99m-LSA and Tc-99m-MSA metabolites were examined. Both Tc-99m-LSA and Tc-99m-MSA showed high liver uptakes. RITC-LSA was taken up by hepatocytes whereas FITC-MSA was taken up by Kupffer cells and endothelial cells. Tc-99m-MSA showed higher spleen and kidney uptakes than Tc-99m-LSA. Tc-99m-LSA metabolites excreted in urine and feces accounted for 44.4 and 50.0% of Tc-99m-LSA injected, respectively, while Tc-99m-MSA metabolites accounted for 51.5 and 10.3%, respectively. In conclusion, LSA is specifically taken up by hepatcytes while MSA by Kupffer cells and endothelial cells. After taken up by the liver, LSA is metabolized by the hepatocytes and then excreted through both the hepatobiliary tract and kidney, whereas MSA is metabolized by Kupffer cells and endoghelial cells and then excreted mainly through the kidney.