The general aim of the proposed plan is to test the safety and efficacy of existing and novel iron chelates applied to contrast enhancement in NMR imaging.
Specific aims are to: 1) select candidate pharmaceuticals from iron chelates of the hydroxamate and catecholate classes; 2) perform a structure-relaxivity analysis of selected iron chelates; 3) evaluate toxicity, mass balance, metabolic fate, distribution, kinetics, and tissue proton relaxation of candidate pharmaceuticals; and 4) assess the diagnostic efficacy of image contrast alteration with such agents in normal and diseased states of experimental animals. Methodologies include skills from the basic scientific disciplines of mathematics, chemistry, electrical engineering and computer sciences and from the biomedical disciplines of pharmacology, immunology, nephrology, gastroenterology, cardiology and neurology. Specific techniques that will be emphasized include pulsed nuclear magnetic resonance analysis, nuclear magnetic resonance imaging and radiotracer detection. Experimental models of neoplastic, inflammatory and vascular diseases will be studied. Included within this group will be experiments to evaluate tumor enhancement with paramagnetic tumor-associated monoclonal antibodies. Agents undergoing urinary, reticuloendothelial and hepatobiliary clearance will be examined. Long-term objectives and the relation to health care are to develop safe, efficacious NMR imaging pharmaceuticals, to identify circumstances under which such agents may improve diagnosis, and to promote further development of iron chelating ligands.
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