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

• Published in: Cancer biotherapy & radiopharmaceuticals Vol. 15; no. 5; pp. 507 - 515
• Main Authors: ROSEBROUGH, S. F, HARTLEY, D. F
• Format: Journal Article
• Language: English
• Published: Larchmont, NY Liebert 01.10.2000
• Subjects: Animals; Antibodies, Monoclonal - pharmacokinetics; Antineoplastic agents; Biological and medical sciences; Chemotherapy; Fab; Galactose - analogs & derivatives; Galactose - pharmacokinetics; galactose receptors; Immunoglobulin Fab Fragments - metabolism; Indicators and Reagents - pharmacokinetics; isothiocyanate; Isothiocyanates - pharmacokinetics; Kidney - diagnostic imaging; Kidney - metabolism; Liver - diagnostic imaging; Liver - metabolism; Male; Medical sciences; Myocardium - metabolism; Pharmacology. Drug treatments; Rabbits; Radionuclide Imaging; streptavidin; Streptavidin - pharmacokinetics; Tissue Distribution; trigalactose; Urinary Bladder - metabolism; Delivery system; Radiolabelling; Controlled release form; Rabbit; Biotin; Monoclonal antibody; Lagomorpha; Vertebrata; Chemotherapy; Target; Mammalia; Animal; Organic isothiocyanate; Diagnosis; Conjugated compound; Galactose; Pharmacokinetics; Labelled compound
• ISSN: 1084-9785; 1557-8852
• DOI: 10.1089/cbr.2000.15.507

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.