Asialoglycoprotein-receptor-targeted hepatocyte imaging using 99mTc galactosylated chitosan

This study investigated the usefulness of Tc-99m hydrazinonicotinamide-galactosylated chitosan (HGC) in hepatocyte imaging. HGC was obtained by coupling the galactose moiety, of both lactobionic acid and succinimidyl 6-hydrazinonicotinate hydrochloride (succinimidyl HYNIC). The coupled product was then radiolabeled with Te-99m using stannous chloride and tricine as reducing agent and coligand, respectively. Labeling efficiency was > 90% both in room temperature and in serum up to 24 h after injection. The hepatic uptake propel-ties of Tc-99m HGC were studied in Balb/C mice. Te-99m HGC and Tc-99m hydrazinonicotinamide chitosan (HC) were intravenously injected into mice, with receptor binding identified by coinjection with 9 and 14 mg of free galactose. Images were acquired with a gamma-camera. After injection via the tail vein of the mice, Tc-99m HGC showed high selectivity for the liver, while Tc-99m HC without a galactose group showed low liver uptake. In addition, the hepatic uptake of Tc-99m HGC was blocked by coinjection of free galactose. Tissue distribution was determined at three different times (10, 60 and 120 min). The liver accumulated 13.16 +/- 2.72%, 16.11 +/- 5.70% and 16.55 +/- 2.28% of the injected dose per gram at 10, 60 and 120 min after injection, respectively. Tc-99m HGC showed specific and rapid targeting of hepatocytes. It is a promising receptor-specific radiopharmaceutical with potential applications in liver imaging for the evaluation of hepatocytic function. (c) 2006 Elsevier Inc. All rights reserved.