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

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.

Two-step immunological approaches for imaging and therapy.

Radiolabeled monoclonal antibodies and their F(ab')2 and Fab fragments have been successful for imaging and therapy. However, their prolonged circulation and nonspecific accumulation in metabolic organs have resulted in high background radioactive levels and delayed imaging times. Current approaches are two- and three-step procedures consisting of first, the injection of a targeting moiety, which has specific binding affinity for both a lesion and a small molecular weight radiolabeled agent, and, second, a subsequently injected radioactive diagnostic or therapeutic agent.

Biochemical modification of streptavidin and avidin: in vitro and in vivo analysis.

Unlabelled: The high affinity streptavidin (or avidin)/biotin system is being investigated for imaging and radiotherapy procedures. Streptavidin (SA) and avidin exhibit markedly different pharmacokinetics, with avidin clearing from the blood much faster than SA. To optimize blood clearance kinetics, SA and avidin were biochemically modified and analyzed in vitro and in vivo.

Galactose-modified streptavidin-GC4 antifibrin monoclonal antibody conjugates: application for two-step thrombus/embolus imaging.

Diagnostic and therapeutic procedures utilizing the high affinity streptavidin (SA)/biotin system are being investigated for in vivo use. We are developing a rapid two-step imaging technique for the diagnosis of deep venous thrombosis and pulmonary embolism. The optimal SA-bound targeting moiety would circulate adequately for sufficient lesion accumulation, but nonbound reagent would clear in a reasonably short time before the injection of radiolabeled biotin.