title: Fluorine-18 labeled galactosylated chitosan for asialoglycoprotein-receptor-mediated hepatocyte imaging.
abstract: 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-(18)F-fluorobenzoate ([(18)F]SFB) under a slightly basic condition. After rapid purification with HiTrap desalting column, [(18)F]FB-GC was obtained with high radiochemical purity (>97%) determined by radio-HPLC. The total reaction time for [(18)F]FB-GC was about 150 min. Typical decay-corrected radiochemical yield was about 4-8%. Ex vivo biodistribution in normal mice showed that [(18)F]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 [(18)F]FB-GC significantly declined in all selected time points. The better liver retention properties of [(18)F]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.
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, 19 Xinjiekou Outer St., Beijing 100 875, China.
authors.forename: Wenjiang
authors.initials: W
authors.lastname: Yang
authors.forename: Tiantian
authors.initials: T
authors.lastname: Mou
authors.forename: Wenyan
authors.initials: W
authors.lastname: Guo
authors.forename: Huihui
authors.initials: H
authors.lastname: Jing
authors.forename: Cheng
authors.initials: C
authors.lastname: Peng
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Zhang
authors.forename: Yunchuan
authors.initials: Y
authors.lastname: Ma
authors.forename: Boli
authors.initials: B
authors.lastname: Liu
mesh_terms: D000818:Animals; D037263:Asialoglycoprotein Receptor / Q000378:metabolism*; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry*; D005462:Fluorine Radioisotopes / Q000737:chemistry; D006031:Glycosylation; D022781:Hepatocytes / Q000378:metabolism; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism*; D051379:Mice; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D037263:Asialoglycoprotein Receptor; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D048271:Chitosan