Hepatocyte-targeted nuclear imaging using ^99mTc-galactosylated chitosan: Conjugation, targeting, and biodistribution

Galactosyl-methylated chitosan (GMC) is a galactosylated chitosan (GC) that is chemically modified to improve labeling efficiency with ^99mTc compared with native GC. The aim of this study was to investigate the possibility of liver-targeted nuclear imaging with ^99mTc-GMC bound to asialoglycoprotein receptors (ASGP-R). Methods: GMC was obtained after the coupling of lactobionic acid, as the galactose moiety, and methyl iodide with chitosan. Using GMC-labeled fluorescein isothiocyanate (FITC-GMC), we examined whether GMC was localized in hepatocytes. After injection via the tail vein of mice with ^99mTc-GMC and galactose-free ^99mTc-methylated chitosan (MC), images were acquired with a γ-camera equipped with a pinhole collimator. Biodistribution was obtained from 10, 60, and 120 min after injection. Results: The composition of galactose groups in GC and tri-, di-, and monomethylated GC was confirmed by nuclear magnetic resonance spectroscopy. FITC-GMC was primarily positioned in hepatocytes, and not in Kupffer cells, of the mouse with a scattered pattern. The γ-camera images showed rapid localization of ^99mTc-GMC to liver. The percentage injected doses per gram (%ID/g) of liver were 11.155 ± 2.332, 14.018 ± 6.081, and 14.082 ± 1.670 %ID/g (mean ± SD) at 10, 60, and 120 min after injection, respectively. By contrast, galactose-free ^99mTc-MC accumulated faintly in the liver. Conclusion: ^99mTc-GMC specifically localized to the liver except for the kidneys in the mouse. GMC may be used to target the ASGP-R on the hepatocytes for nuclear imaging.