RADIORHENIUM ANTIBODIES FOR RADIOIMMUNOTHERAPY

THE OBJECTIVE OF THIS PHASE I SBIR PROJECT IS TO DEVELOP A RE-186 AGENT SUITABLE FOR LABELING BIFUNCTIONAL CHELATING AGENT ANTIBODY CONJUGATES. ALTHOUGH CHEMICALLY SIMILAR TO TC-99M, APPLICATION OF RE-186 TO YIELD POTENTIAL THERAPEUTIC RADIOPHARMACEUTICALS PRESENTS PROBLEMS WHICH HAVE YET TO BE SOLVED. SPECIFICALLY, IT IS MUCH MORE DIFFICULT TO MAINTAIN RE IN REDUCED OXIDATION STATES THAN TC, AND THUS RE-LABELED AGENTS HAVE A GREATER TENDENCY TO REVERT TO PERRHENATE. ALSO, LIGAND EXCHANGE REACTIONS ON RE PROCEED MORE SLOWLY THAN DO ANALOGOUS REACTIONS ON TC, AND CONDITIONS USED FOR THE LIGAND EXCHANGE SYNTHESIS OF RE-186 ANTIBODY CONJUGATES WILL HAVE TO BE DEVELOPED TO ALLOW EXCHANGE WHILE PREVENTING LOSS OF REACTIVITY. IN THIS PROJECT WE WILL DEVELOP SEVERAL PROCEDURES NEEDED FOR THE LABELING OF PROTEIN CONJUGATES WITH RE-186. THESE WILL INVOLVE REDUCTION OF PERRHENATE USING AGENTS SUCH AS SN(II), AS WELL AS LIGAND EXCHANGE PROCEDURES USING RE-186 COMPLEXES SUCH AS AND RE-CITRATE. INITIAL EXPERIMENTS WILL BE CONDUCTED WITH THE FREE BIFUNCTIONAL LIGAND, AND SUBSEQUENT EXPERIMENTS WILL UTILIZE THE ANTIBODY CONJUGATES WHICH ARE ALREADY AVAILABLE. LABELING YIELDS WILL BE MONITORED BY HPLC TECHNIQUES. IN VITRO IMMUNOREACTIVITY ASSESSMENT WILL BE DONE TO ASSESS THE EFFECTS OF RADIOLABELING AND CONJUGATION ON ANTIBODIES. THE ABILITY TO LABEL ANTIBODIES WITH RE-186 IS THE FIRST STEP TOWARDS DEVELOPING A RE-186 RADIOIMMUNOTHERAPEUTIC AGENT.