Stability studies on "3+1" mixed-ligand technetium and rhenium complexes

The stability and reactivity of "3+1" ^99mTc mixed-ligand complexes were investigated in vitro and in vivo in the blood of rats. Surprisingly, in whole blood the complexes, which proved to be stable in saline, PBS of pH 7.4 and mostly in plasma, were converted into more hydrophilic metabolites. Small structural differences in the complex molecule have a profound influence on the rate of metabolism of the complexes. Transchelation reactions with glutathione (GSH) were hypothesized and this hypothesis substantiated by challenge experiments. Structural parameters influencing the stability of the complexes and consequences for the radiopharmaceutical design are discussed.