Studies on phosphine and phosphonite cationic technetium complexes as potential myocardial imaging agents

The ultimate goal of this research is the development of a more effective 99m-Tc myocardial imaging agent. In this thesis the disciplines of bioanalytical chemistry and inorganic chemistry are combined and employed to gain a further understanding of the in vivo behavior of potential 99m-Tc myocardial imaging agents. Analytical methods, particularly high performance liquid chromatography (HPLC), are used to investigate the in vitro behavior of the cationic 99m-Tc complexes and to relate this behavior to trends seen during in vivo testing.; Due to the low molar concentrations of 99m-Tc radiopharmaceuticals, HPLC with radiometric detection is one of the few means available for their analysis and characterization. Reverse phase ion-pair HPLC is the preferred method of analysis for cationic 99m-Tc complexes. Studies are presented which elucidate some of the unusual chromatographic behavior seen during the reverse phase HPLC analysis of these complexes. Analyses of unstable complexes which are susceptible to in vivo redox reactions at the 10{dollar}sp{lcub}-10{rcub}{dollar} to 10{dollar}sp{lcub}-15{rcub}{dollar} M concentration level are described.; In vitro prescreening of potential 99m-Tc radiopharmaceuticals is essential to the development of these agents. New analytical techniques are presented which may prove of use in the development of prescreening methods. In vitro chromatographic analysis of the serum protein binding behavior of some cationic 99m-T complexes provides an explanation of the unusual biological properties of these complexes.; The synthesis of two groups of 99-Tc and 99m-Tc complexes are described. The first group is based upon bidentate phosphonite ligands which are analogs to the DMPE (bis-1,2-dimethylphophinoethane) ligand. The second group is based upon mixed ligand complexes containing the bidentate phosphine ligand DMPE and either monodentate phosphines or isonitriles; Tc(L){dollar}sb2{dollar}(Y){dollar}sb2sp+{dollar} where L = DMPE, and Y = a monodentate phosphine or isonitrile ligand. These complexes were synthesized to both further our understanding of the biological behavior of cationic 99m-Tc myocardial imaging agents, and assist in the development of prescreening methods.