Tc-Hydrazinonicotinamide-galactosyl-chitosan

Asialoglycoprotein (ASGP) is specifically taken into mammalian hepatocytes by binding to ASGP receptors (ASGP-Rs) (1). The galactosyl moiety of ASGP is recognized on the surface of hepatocytes and is bound by ASGP-R. The ASGP–ASGP-R complex on the cell surface is subsequently taken into cytoplasm by endocytosis and transferred to lysosomes. ASGP-R is then dissociated from ASGP and recycled to the cell surface. ASGP is degraded in the lysosomes and excreted into the bile. The number of ASGP-Rs on the hepatocytes of individuals with liver disease decreases and is thus considered a good indicator for the evaluation of liver function. Because ASGP-R recognizes galactose, Tc-diethylenetriamine pentaacetic acid-galactosyl-human serum albumin (Tc-GSA) (2, 3) and Tc-galactosyl-neoglycoalbumin (Tc-NGA) (4) are ASGP-R probes that accumulate specifically in the liver and are used for liver scintigraphy to determine liver mass and function. Chitosan is a linear polysaccharide composed of D-glucosamine and -acetylglucosamine subunits with numerous amine groups of D-glucosamine for ligand conjugation. Kim et al. (5) conjugated hydrazinonicotinamide (HYNIC) and galactose ( lactobionic acid) to deacetylate chitosan for radiolabeling with Tc to form Tc-HYNIC-galactosyl-chitosan (Tc-HGC) for imaging ASGP-R expression in the liver.