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

This study investigated the usefulness of ^99mTc 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 ^99mTc 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 properties of ^99mTc HGC were studied in Balb/C mice. ^99mTc HGC and ^99mTc 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 γ-camera. After injection via the tail vein of the mice, ^99mTc HGC showed high selectivity for the liver, while ^99mTc HC without a galactose group showed low liver uptake. In addition, the hepatic uptake of ^99mTc 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. ^99mTc 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.