Isothiocyanate-trigalactose: Application for antibody-targeted delivery ofdiagnostic and therapeutic agents

Radiolabeled monoclonal antibodies (MAb) and MAb-streptavidin conjugates ex hibit slow blood clearance which impedes radioimmunoimaging and radioimmuno therapy. To control blood clearance and lower background levels, lesion-spe cific targeting proteins can be modified with galactose derivatives for liv er uptake via the hepatocyte galactose receptor. In this study, an isothioc yanate-trigalactose derivative (ITC-Tgal) designed for direct coupling to p rotein amino groups, was synthesized and characterized. In vitro experiment ation demonstrated efficient conjugation of ITC-Tgal to streptavidin (SA) a nd 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 i ncreased blood clearance with the liver uptake and the rate of blood cleara nce controlled by the extent of ITC-Tgal modification.