Preparation and biological evaluation of radiolabelled antibodies with selected carbohydrate modifications.
Two carbohydrates, N-acetylgalactosamine (GalNAc) and galactose-beta-1,3-GalNAc have been attached to human IgG (hIgG) by a novel linking reagent, hexafluoroglutaric acid dimethyl ester. Fluorine-19 NMR signals were used for the determination of the conjugation ratio. A third carbohydrate, sialic acid, was conjugated via reductive amination and the conjugation ratio determined by a resorcinol assay. The biological behaviour of these radioiodinated antibodies with carbohydrate modifications in normal mice indicates an enhanced liver uptake at 15 min post-injection with an associated change in circulating blood levels occurs for the galactose-based hIgG preparations. However, no significant differences in the biodistribution were observed for the sialic acid conjugate. These studies confirm the potential of carbohydrate-antibody conjugation for modifying the behaviour of antibodies in immunoscintigraphy and radioimmunotherapy.
Faculty of Pharmacy, University of Alberta, Edmonton, Canada.
P
P
Qi
T R
TR
Sykes
R R
RR
Koganty
S
S
Selvaraj
A A
AA
Noujaim
D000818:Animals; D002240:Carbohydrate Sequence; D002241:Carbohydrates / Q000737:chemistry* / Q000493:pharmacokinetics*; D004353:Drug Evaluation, Preclinical; D005977:Glutarates / Q000737:chemistry; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism; D000922:Immunotoxins / Q000737:chemistry* / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007553:Isotope Labeling / Q000379:methods*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008954:Models, Biological; D008969:Molecular Sequence Data; D014018:Tissue Distribution; D005466:Fluorocarbons
D002241:Carbohydrates; D005977:Glutarates; D007074:Immunoglobulin G; D000922:Immunotoxins; D007457:Iodine Radioisotopes; C081499:dimethyl hexafluoroglutarate; D005466:Fluorocarbons