The goals of this project have been to design, synthesize and evaluate new compounds as potential organ- or tumor-imaging agents. Pharmacological and biochemical principles have served as the basis for achieving site-specific delivery of these agents. Current research is focused on the synthesis of radioiodinated and polyiodinated analogs of naturally-occurring lipids as potential scintigraphic agents and radiopaques, respectively. Of especial interest are iodinated analogs of fatty acids, acylcarnitines, sterol esters, diacyglycerides, triglycerides, phospholipid ethers, and phospholipids. The target compounds will be designed so as to provide information not only on the ability of these agents to accumulate in specific tissues but also on their capacity to participate in biochemical transformations peculiar to such tissues. Accordingly, such probes offer the potential of furnishing a noninvasive means for ascertaining both organ structure and function. All new agents will be labeled with iodine-125 for initial biodistribution studies in normal rats. Promising agents will then be followed up by Gamma-camera scintigraphy and computed tomography in the appropriate rat or rabbit model. Selected agents will also be incorporated into natural or reconstituted lipoproteins in order to capitalize on the known biodistribution properties of these macromolecular vesicles. Such research holds significant promise for the eventual development of new radiologic agents for the diagnosis of various hepatic, endocrine, and cardiovascular disorders.
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