THE OBJECTIVE OF THIS PROJECT IS TO DEVELOP TECHNIQUES FOR USING MONOCLONAL ANTIBODIES LABELED WITH 212BISMUTH, AN ALPHA PARTICLE-EMITTING RADIONUCLIDE, AS IN VITRO OT IN VIVOCYTOTOXIC AGENTS.

THE OBJECTIVE OF THIS PROJECT IS TO DEVELOP TECHNIQUES FOR USING MONOCLONAL ANTIBODIES LABELED WITH 212BISMUTH, AN ALPHA PARTICLE-EMITTING RADIONUCLIDE, AS IN VITRO OT IN VIVOCYTOTOXIC AGENTS. ANTIBODY CONJUGATES WILL BE DEVELOPED FORRADIOIMAGING TO LOCALIZE TO THE TUMOR SITE ONLY, WITH MINIMAL UPTAKE BY THE RETICULOENDOTHELIAL SYSTEM, MAKING THEM IDEAL AGENTS FOR IMMUNOTHERAPY. THIS SITE-SPECIFIC COVALENT ATTACHMENT OF CHELATORS TO THE OLIGOSACCHARIDES IN THE CONSTANT REGION, AWAY FROM THE ANTIBODY'S BINDING SITE, YIELDS HOMOGENEOUS CONJUGATES THAT RETAIN THEIR ANTIGEN BINDING ACTIVITY AND AFFINITY. THESE CHEMICAL TECHNIQUES ARE AN IMPROVEMENT OVER EXISTING METHODS FOR ANTIBODY MODIFICATION. 212BISMUTH HAS BEEN CHELATED BY DTPA COVALENTLY ATTACHED TO MONOCLONAL ANTITUMOR ANTIBODIES BY THE ABOVE METHODS. IN THIS PHASE I PROJECT, THE RESEARCH WILL DEMONSTRATE IMMUNOSPECIFIC KILLING OF TUMOR CELLS IN VITRO AND STABILITY OF THE MAB-DTPA-212BI CONJUGATE IN VIVO.IN PHASE II, RADIOIMMUNOTHERAPY MAY BE ACHIEVED IN AN IN VIVO MURINE TUMOR MODEL. ANTIBODY LOCALIZATION WILL BE STUDIED AND THERAPEUTIC EFFECTS ASSESSED. THE ULTIMATE GOALOF RADIOIMMUNOTHERAPY IS THE TREATMENT OF HUMANS FOR CANCER.