THE CHEMISTRY OF TECHNETIUM RELATED TO NUCLEAR MEDICINE

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The aims of this research are to investigate further the uses of technetium complexes containing substituted isonitrile ligands in routine clinical nuclear medicine. The objective is to capitalize upon technology originally developed in these laboratories that has since led to the clinical trials of a new myocardial perfusion agent (99mTc-MIBI) now underway in U.S. and European medical centers. The isonitrile class of compounds in principle constitute a very large number of different chemical species with widely differing biological distribution properties. This is possible because the ligands (CN-R) are carbon-bonded to the central metal atom, thus allowing the nature of the inner coordination sphere of the complexes to be modified by varying the substituent R group. To investigate the full potential of this class requires a combination of chemical, biochemical and biological studies at both macroscopic and tracer concentrations using the long-lived radionuclide Tc-99 and the short-lived gamma emitter Tc-99m. This proposal describes, therefore, a program to synthesize and characterize technetium complexes containing a variety of substituted isonitrile ligands and to evaluate their potential as new radiopharmaceuticals. The procedures will include complete chemical identification of the compounds at carrier added levels and transfer of the chemistry to no carrier added concentrations for biological evaluation. This portion of the research will involve developing new methods of synthesis and analysis, so that structure-activity relationships can be examined by in vivo and in vitro studies using well-defined chemical species. The mechanisms of action of those members of the class that have already been shown to be effective for imaging the human heart will be examined. In addition, other applications of this versatile series of complexes will be investigated, for example, cardiac agents that reflect processes other than simple perfusion and radiopharmaceuticals for studying lung, hepatobiliary, and renal function.