STUDIES OF TECHNETIUM AND RHENIUM DIPHOSPHINE COMPLEXES, AND SOME CATIONIC TECHNETIUM COMPLEXES OF SCHIFF BASE LIGANDS, AS MYOCARDIAL IMAGING AGENTS (RADIOPHARMACEUTICALS).

摘要

The ultimate goal of this research is the development of an efficacious ('99m)Tc myocardial imaging agent. This thesis describes (i) the application of inorganic and analytical techniques to the preparation and characterization of cationic technetium-99 and rhenium complexes in macroscopic amounts, and (ii) the preparation and biological evaluation of these, and other, complexes using ('99m)Tc and ('186)Re at the very low concentrations of these isotopes encountered in nuclear medicine.;Cationic diphosphine complexes of technetium were prepared in the V, III and I oxidation states. The Tc(V) and Tc(III) complexes can be represented as tr- TcD(,2)Y(,2) ('+) where D is a diphospine such as 1,2-bis(dimethylphosphino)ethane and Y is O, Cl, Br, or I. The Tc(I) complex can be represented as TcD(,3) ('+). Analogous rhenium complexes in the III and I states were also prepared using both nonradioactive rhenium and ('186)Re. These cationic complexes, prepared with ('99m)Tc, were evaluated as myocardial imaging agents in different animal models. In vivo evaluation of the ('186)Re-diphosphine analogs has provided insight into the role played by oxidation-reduction processes in determining myocardial accumulation of the ('99m)Tc-diphosphine complexes.;A novel class of cationic ('99m)Tc radiopharmaceuticals has been prepared using tetradentate Schiff base ligands. The Tc(V) parent complexes, ('99m)TcLO ('+) (L = tetradentate Schiff base), form cationic Tc(III) mixed ligand complexes upon reaction with monodentate phosphines, phosphites or isonitriles (as for example, tr- ('99m)TcL(PR(,3))(,2) ('+)). The properties of these complexes can be readily varied over wide ranges by altering the nature of the equatorial Schiff base and/or the axial monodentate ligands. In vivo evaluation of selected complexes indicates definite myocardial uptake and it is very likely that one member of this new class of cationic ('99m)Tc mixed ligand complexes will be an efficacious myocardial imaging agent.;The ('99)Tc and Re complexes have been characterized by classical chemical techniques including (1) single-crystal x-ray analysis, (2) elemental analysis, (3) spectroscopy (IR, visible-UV, and/or NMR), (4) extended x-ray absorption fine structure analysis (EXAFS), (5) electrochemistry, and (6) high performance liquid chromotography analysis (HPLC). The ('99m)Tc complexes have been characterized by comparison of their HPLC retention times with the retention times of standard solutions of their ('99)Tc analogues. Thus HPLC comprises the link between macroscopic ('99)Tc chemistry and microscopic ('99m)Tc chemistry.