In this application, the broad long-term objective of this project continues to be preparation of site specific technetium radiopharmaceuticals which would permit new or improved quantitative in vivo studies of physiological and biological processes. In carrying out this objective, we utilize the diaminedithiol (DADT) ligand system developed under this grant which has proved to be a multi-purpose chelate for the preparation of new technetium complexes, and adopted by a number of research groups world-wide in their own research endeavors. We have made significant progress in understanding the structural chemistry of these complexes as it becomes necessary in order to investigate the general relationship of their structure to their observed vitro and in vivo behavior. The development of a neutral and lipid-soluble technetium-99m complex with biophysical properties appropriate for studies focused on receptor mediated processes would permit widespread studies at the community hospital level similar to those performed on a more limited basis with carbon-11 and iodine-123 tracers. Thus, we have chosen to focus our proposed neuroreceptors. In accomplishing this goal, we will validate and extend the use of spectroscopic trends for analytical characterization of the Tc-DADT complexes, and assess the utility of a newly developed neutral bifunctional chelate in the synthesis of potential receptor-binding complexes.
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