The overall aim of the proposed renewal is to test, in preclinical and in clinical experiments, the safety and efficacy of iron- containing pharmaceuticals for obtaining added information from magnetic resonance imaging and spectroscopy.
The specific aims are threefold. First, study of newly selected agents will be undertaken by (a) screening selected paramagnetic iron chelates of hydroxamate, catecholate, phenolate and hydroxpyridonate ligands; and (b) exploring paramagnetic and superparamagnetic particulates. Second, continued study of selected agents from years 01-03 is proposed by (a) clinically measuring elimination, metabolic fate, and pharmacokinetics for agents from three biodistribution classes (ferrioxamine B, Fe-HBED, and magnetic AMI-25); (b) clinically assessing safety and efficacy of Fe-HBED and ferrioxamine B; (c) comparatively evaluating different enhancement agents for diagnosis of focal hepatic disease, and (d) comparatively evaluating efficacy of different relaxation agents for 31P MRS signal localization and enhancement. Third, the added benefit of T2, T2- and susceptibility-sensitive imaging techniques will be studied. By obtaining this data, progress will be made toward more complete understanding of magnetic resonance technology. Practical agents for image enhancement in several organ systems will be introduced. More refined uses, some previously considered poorly feasible, will be developed for spectroscopy and for tumor-, inflammation-, and flow-targeting. Investigative methods include (a) chemical synthesis and analysis; (b) pharmaceutical formulation and quality assurance; (c) nuclear magnetic resonance imaging, spectroscopy, and relaxometry; and (d) nuclear medicine radioanalogue detection methods.
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