RADIOIODINATED CONJUGATES FOR THERAPY AND DIAGNOSIS

THE PURPOSE OF THIS CONTRACT PROPOSAL IS TO DEVELOP NEW RADIOIODINE-LABELED CONJUGATES FOR MONOCLONAL ANTIBODIES THAT CAN BE USED IN DIAGNOSIS AND THERAPY OF CANCER. THE GOAL OF OUR PROPOSED RESEARCH IS TO INVESTIGATE A NOVEL METHOD OF INTRODUCING HIGH SPECIFIC ACTIVITY RADIOIODINE INTO SOME SMALL MOLECULES WHICH CAN BE CONJUGATED TO MONOCLONAL ANTIBODIES. OUR APPROACH TO DEVELOP NEW CONJUGATES IS PATTERNED AFTER THE COMMERCIALLY AVAILABLE BOLTON-HUNTER AND WOOD'S REAGENTS, WHERE THE RADIOIODINATIONS ARE CARRIED OUT IN A SEPARATE REACTION VESSEL SO THAT THE ANTIBODY IS NOT EXPOSED TO THE HARSH OXIDIZING CONDITIONS OF THE RADIOIODINATION. ONE IMPORTANT DIFFERENCE BETWEEN THE MENTIONED REAGENTS AND THE REAGENTS THAT WE WILL BE RADIOIODINATING IN OUR PROPOSED STUDIES IS THAT THE RADIOIODINE WILL BE ATTACHED TO A NONACTIVATED AROMATIC RING. THIS SHOULD IMPART AN INCREASED STABILITY AGAINST CHEMICAL AND ENZY-MATIC DEGRADATION. THIS PHASE I STUDY WILL INCLUDE THE SYNTHESIS OF TARGETED COMPOUNDS, STUDIES OF RADIOIODINATION REACTION CONDITIONS, AND STUDIES LEADING TO EVENTUAL RADIOPHARMACEUTICAL ""KIT'' FORMULATIONS.