SBIR-STTR Award

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.Awardee's statement of the potential commercial applications of the research:The U. S. market for all contrast agents will exceed $2 billion by 1994. Magnetic resonance image contrast enhancers represent the fastest growing segment of this market. There is presently no macromolecular imaging agent on the market, in spite of considerable research efforts in this area. A safe and efficacious contrast agent which remains in the vascular compartment will rapidly establish a sizeable market niche.National Cancer Institute (NCI)

Biomedical Frontiers, Inc. (BMF) has shown that non-toxic, macromolecular iron chelates can be produced by the covalent attachment of deferoxamine to biocompatible polymers and the subsequent addition of iron. Based on preliminary animal studies, these chelates show considerable promise as non-toxic contrast enhancing agents for use m magnetlc resonance imaging. There is currently a profound need for a safe and efficacious contrast agent for the advancement of MR imaging of the gastrointestinal tract, the urinary system and the vascular system. The compounds being developed by BMF are excellent candidates for the improved utility and diagnostic capabilities of MRI in these tree areas. BMF proposes to synthesize and characterize a variety of these polymer-ferrioxamine derivatives, perform preclinical toxicology, and initiate clinical trials for safety and efficacy with one or more of these compounds. With the evolution of MRI as a primary modality in the radiologist's armentarium, a clear need has been demonstrated for agents that improve the diagnostic image. Initial studies in licate that the macromolecular chelates will be safe and efficacious contrast agents for specific MRI applications, and therefore will have significant commercial application.Awardee's statement of the potential commercial applieations of the research:There is a clinical need for safe and reasonably priced oral and vascular contrast agents. Despite extensive research efforts in several corporate and academic research laboratories, there is little evidence that this type of macromolecular contrast agents are near commercialization. The products under development by Biomedical Frontiers do address the clinical needs and therefore represent a significant market opportunity.National Institute of Diabetes and Digestive and Kidney Diseases NIDDK)