Studies on some technetium and rhenium compounds: Bridging inorganic chemistry and nuclear medicine.

摘要

The purpose of this dissertation was to study the basic chemistry of some technetium(V) and rhenium(V) compounds as well as the biodistributions of the novel {dollar}sp{lcub}rm 99m{rcub}{dollar}Tc(V) compounds.; New classes of tetradentate-N{dollar}sb2{dollar}S{dollar}sb2{dollar} and tetradentate-N{dollar}sb4{dollar} ligands which contain 5,7,5-membered ring chelate system have been used in this study. The presence of the 7-membered chelate ring provides synthetic flexibility for the attachment of different side-chain substituents, and thus for a ready route to control the biodistribution of the resulting {dollar}sp{lcub}rm 99m{rcub}{dollar}Tc radiopharmaceutical.; The labelling of the new ligands with {dollar}sp{lcub}rm 99m{rcub}{dollar}Tc results in a single radiochemical product, or the expected stereoisomeric products. Analytical data indicate that all the novel N{dollar}sb2{dollar}S{dollar}sb2{dollar} and N{dollar}sb4{dollar} ligands form a tetradentate 5,7,5-membered ring chelate system with mono-oxo Tc(V) or Re(V) core: (M(V)OL) {dollar}sp{lcub}rm x{rcub}{dollar} (M = Tc(V) or Re(V); L = tetradentate N{dollar}sb2{dollar}S{dollar}sb2{dollar} or N{dollar}sb4{dollar} ligands; x = 0 or {dollar}-{dollar}1).; The inert "yl" oxygen undergoes slow oxygen exchange with free water in alkaline solution. The stoichiometry of the five-coordinate complexes (ReO(DADS)) {dollar}sp-{dollar}, (ReO(DBDS)) {dollar}sp-{dollar} and (TcO(DBDS)) {dollar}sp-{dollar} plus the observed rate law imply an associative mechanism.; In rat biodistribution studies, the DBDS and DADS complexes show very similar biological activity with rapid blood and renal clearance. Phenyl substituents on the 7-membered ring give rise to {dollar}sp{lcub}rm 99m{rcub}{dollar}Tc complexes of increased lipophilicity, increased liver uptake, and minimal hepatobiliary clearance. (Tc(V)ON{dollar}sb4{dollar}) {dollar}sp0{dollar} complexes with phenyl substituents on the 7-membered ring exhibit limited brain uptake.