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The stability and reactivity of mixed-ligand  99m Tc complexes of the general formula [ 99m TcOL 1 L 2 ], where L 1 H 2  is either an N-substituted bis-(2-mercaptoethyl)amine [SNMeS] or 3-thiapentane-1,5-dithiol [SSS] and L 2 H is a monodentate thiol [RS], were investigated. The complexes undergo transchelation reactions with glutathione and other SH-group containing blood constituents. The reactions are reversible and can be inhibited by addition of diethylmaleate. Challenge experiments were performed with a broad set of  99m Tc 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 glutathione depends on the donor set of the tridentate ligands as well as the structure of the monodentate ligands. Especially the stability of complexes containing 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 performance.

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