MACROMOLECULAR CONTRAST AGENTS FOR MAGNETIC RESONANCE

BIOMEDICAL FRONTIERS (BMF) HAS ESTABLISHED THAT THE IRON CHELATOR, DEFEROXAMINE, CAN BE COVALENTLY BOUND TO POLYMERS AND HAS DEMONSTRATED, IN PRECLINICAL STUDIES, THAT THESE CONJUGATES CAN BE USED THERAPEUTICALLY AS ANTIOXIDANTS. WE WILL EVALUATE THESE COMPOUNDS, FOLLOWING SATURATION WITH FERRIC IRON, AS PARENTERAL MAGNETIC RESONANCE IMAGE (MRI) CONTRAST ENHANCERS. THE DIAGNOSTIC ACCURACY OF MRI IS GREATLY IMPROVED BY USING CONTRAST ENHANCERS. PRESENTLY USED, LOW MOLECULAR WEIGHT, CONTRAST ENHANCERS CONTAINING THE PARAMAGNETIC GADOLINIUM ION DIFFUSE RAPIDLY FROM THE VASCULAR COMPARTMENT INTO INTERSTITIAL FLUID AND ARE THEREFORE OF LIMITED UTILITY FOR A NUMBER OF IMAGING APPLICATIONS. A NON-TOXIC, MACROMOLECULAR CONTRAST AGENT, WILL IMPROVE RESOLUTION OF VASCULAR PATHOLOGY, PROVIDE INFORMATION ABOUT TISSUE PERFUSION AND MAY INCREASE THE DETECTION SENSITIVITY OF CERTAIN TYPES OF TUMORS. WE WILL, IN COLLABORATION WITH EXTERNAL CONSULTANTS, MEASURE RELAXIVITIES OF THREE CHELATOR-POLYMER CONJUGATES, DETERMINE THE DEGREE OF CONTRAST ENHANCEMENT AND ESTABLISH INITIAL SAFETY MARGINS IN ANIMALS. ASSUMING THAT THIS FEASIBILITY STUDY DEMONSTRATES THAT THESE COMPOUNDS ARE NON-TOXIC AND YIELD SIGNIFICANTLY ENHANCED IMAGE CONTRAST, WE WILL BE IN A POSITION TO DEVELOP A DIAGNOSTIC AGENT WITH A SUBSTANTIAL MARKET POTENTIAL.