Fluorine-18 labeled galactosylated chitosan for asialoglycoprotein-receptor-mediated hepatocyte imaging

Galactosylated chitosan (GC) was prepared by reacting lactobionic acid with water-soluble chitosan. GC was labeled with fluorine-18 by conjugation with N-succinimidyl-4-¹⁸F-fluorobenzoate (¹⁸F]SFB) under a slightly basic condition. After rapid purification with HiTrap desalting column, ¹⁸F]FB-GC was obtained with high radiochemical purity (>97%) determined by radio-HPLC. The total reaction time for ¹⁸F]FB-GC was about 150 min. Typical decay-corrected radiochemical yield was about 4–8%. Ex vivo biodistribution in normal mice showed that ¹⁸F]FB-GC had moderate activity accumulation in liver with very good retention (11.13 ± 1.63, 10.97 ± 1.90 and 10.77 ± 0.95% ID/g at 10, 60, 120 min after injection, respectively). The other tissues except kidney showed relative low radioactivity accumulation. The high liver/background ratio affords promising biological properties to get clear images. The specific binding of this radiotracer to the ASGP receptor was confirmed by blocking experiment in mice. Compared with the non-blocking group the hepatic uptake of ¹⁸F]FB-GC significantly declined in all selected time points. The better liver retention properties of ¹⁸F]FB-GC than that of albumin based imaging agents may improve imaging quality and simplify pharmacokinetic model of liver function in the future application with PET imaging.