title: Evaluating the potential of a new isotope-labelled glyco-ligand for estimating the remnant liver function of schistosoma-infected mice.
abstract: A new glyco-derivative compound (OCTAM) was developed and labelled with isotope to form (188) Re-OCTAM as a candidate nuclear medicine imaging agent for testing the liver function. We evaluated the potential of isotope-labelled OCTAM for estimating the remnant liver function in vitro and in vivo schistosoma-infected mice. The affinity of OCTAM to liver asialoglycoprotein receptors (ASGPR) was assessed by competitive inhibition assay in vitro. In vivo assessments were performed to score the remnant liver function in mice at different schistosomal infection stages. OCTAM binds specifically to ASGPR and showed competitive inhibition of anti-ASGPR antibody binding to hepatocytes, and was higher than that of other galactosyl ligands. Micro-SPECT/CT images of uninfected mice revealed strong liver uptake. Quantified serial images of mice infected for 9, 12 and 18 weeks showed delayed liver uptake, and the retention of uptake was inversely correlated with stage and grade of schistosoma infection. Pathological and biochemical analysis demonstrated that gradually accumulating liver injury caused by infection significantly influenced uptake of (188) Re-OCTAM. Hepatic ASGPR expression diminished only in the chronic infection stage. This study demonstrated that the isotope-labelled OCTAM could accumulate in the liver, might have potential as an imaging agent for in vivo hepatic function evaluation of schistosomiasis.
authors.affiliation: Department of Molecular Parasitology and Tropical Diseases, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Center for International Tropical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: P-C
authors.initials: PC
authors.lastname: Cheng
authors.affiliation: Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan.
authors.forename: P-F
authors.initials: PF
authors.lastname: Chiang
authors.affiliation: Institute of Medical Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan.
authors.forename: K-M
authors.initials: KM
authors.lastname: Lee
authors.affiliation: Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan.
authors.forename: C-H
authors.initials: CH
authors.lastname: Yeh
authors.affiliation: Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan.
authors.forename: K-L
authors.initials: KL
authors.lastname: Hsu
authors.affiliation: Chemistry Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan.
authors.forename: S-W
authors.initials: SW
authors.lastname: Liu
authors.affiliation: Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan.
authors.forename: L-H
authors.initials: LH
authors.lastname: Shen
authors.affiliation: Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan.
authors.forename: C-L
authors.initials: CL
authors.lastname: Peng
authors.affiliation: Department of Molecular Parasitology and Tropical Diseases, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Center for International Tropical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: C-K
authors.initials: CK
authors.lastname: Fan
authors.affiliation: Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan.
authors.forename: T-Y
authors.initials: TY
authors.lastname: Luo
mesh_terms: D000818:Animals; D037263:Asialoglycoprotein Receptor / Q000819:agonists*; D004195:Disease Models, Animal; D006020:Glycopeptides / Q000378:metabolism*; D007553:Isotope Labeling; D008099:Liver / Q000000981:diagnostic imaging* / Q000473:pathology; D008111:Liver Function Tests / Q000379:methods*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009683:Nuclear Medicine / Q000379:methods*; D011859:Radiography; D012547:Schistosoma / Q000472:pathogenicity; D012552:Schistosomiasis / Q000175:diagnosis* / Q000473:pathology*
chemical_list: D037263:Asialoglycoprotein Receptor; D006020:Glycopeptides