Reactivity of Tc-99m(V) "3+1"mixed-ligand complexes towards glutathione

The stability and reactivity of mixed-ligand Tc-99m complexes of the genera l formula [(TcOLL2)-Tc-99m-L-1], where (LH2)-H-1 is either an N-substituted bis-(2-mercaptoethyl)amine [SNMeS] or 3-thiapentane-1,5-dithiol [SSS] and (LH)-H-2 is a monodentate thiol [RS], were investigated. The complexes unde rgo transchelation reactions with glutathione and other SH-group containing blood constituents. The reactions are reversible and can be inhibited by a ddition of diethylmaleate. Challenge experiments were performed with a broa d set of Tc-99m mixed-ligand complexes to investigate the influence of both the tridentate ligand and the monodentate ligand on the stability of this type of complex. The occurrence of ligand exchange reactions with glutathio ne depends on the donor set of the tridentate ligands as well as the struct ure of the monodentate ligands. Especially the stability of complexes conta ining a monodentate ligand with an amine nitrogen in the side chain can be increased by lengthening the carbon chain between the sulfhydryl group and the nitrogen. Thus, it might be possible to improve their in vivo performan ce.