title: Isothiocyanate-trigalactose: application for antibody-targeted delivery of diagnostic and therapeutic agents.
abstract: Radiolabeled monoclonal antibodies (MAb) and MAb-streptavidin conjugates exhibit slow blood clearance which impedes radioimmunoimaging and radioimmunotherapy. To control blood clearance and lower background levels, lesion-specific targeting proteins can be modified with galactose derivatives for liver uptake via the hepatocyte galactose receptor. In this study, an isothiocyanate-trigalactose derivative (ITC-Tgal) designed for direct coupling to protein amino groups, was synthesized and characterized. In vitro experimentation demonstrated efficient conjugation of ITC-Tgal to streptavidin (SA) and MAb Fab fragment with a corresponding decrease in protein net charge. In vivo studies were conducted with radiolabeled ITC-Tgal modified and native SA and MAb Fab fragment. ITC-Tgal modified SA and Fab fragment exhibited increased blood clearance with the liver uptake and the rate of blood clearance controlled by the extent of ITC-Tgal modification.
authors.affiliation: Department of Radiology, 601 Elmwood Ave., Box 648, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: S F
authors.initials: SF
authors.lastname: Rosebrough
authors.forename: D F
authors.initials: DF
authors.lastname: Hartley
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics; D005690:Galactose / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D007202:Indicators and Reagents / Q000493:pharmacokinetics; D017879:Isothiocyanates / Q000493:pharmacokinetics; D007668:Kidney / Q000000981:diagnostic imaging / Q000378:metabolism; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D011817:Rabbits; D011877:Radionuclide Imaging; D019809:Streptavidin / Q000493:pharmacokinetics; D014018:Tissue Distribution; D001743:Urinary Bladder / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007202:Indicators and Reagents; D017879:Isothiocyanates; C101225:trigalactose; C037152:isothiocyanic acid; D019809:Streptavidin; D005690:Galactose