Characterization of Technetium-99m Complexes of Pentane-2, 4-dione Bis(N-methylthiosemicarbazone)

Abstract

Further characterization of the two neutral technetium-99m (^99mTc) complexes of pentane-2, 4-dione bis-(N-methylthiosemicarbazone) (PETS) was carried out using a new dianionic PETS derivative, 3, 3-dimethyl-pentane-2, 4-dione bis(N-methylthiosemicarbazone) (DM-PETS), and the well characterized ^99mTc complex of 2, 2, 9, 9-tetramethyl-4, 7-diaza-1, 10-decanedithiol (DADT) as references. While PETS generated two neutral ^99mTc complexes, ^99mTc-PETS-L₁ and ^99mTc-PETS-L₂, by both the stannous reduction method and the ligand exchange reaction with six-coordinated ^99mTc(V) complex of N, N'-ethylenebis(acetylacetone imine), DM-PETS formed only one neutral ^99mTc complex. ^99mTc-PETS-L₂, the more lipophilic complex of the two ^99mTc-PETS, was obtained with a much higher yield than ^99mTc-PETS-L₁ by the ligand exchange reaction of PETS with the five-coordinated ^99mTc(V) complex of glucoheptonate. In addition, while ^99mTc-PETS-L₂ and ^99mTc-DADT remained unchanged in the presence of CN^- anions, a breakdown of the original complexes was observed in ^99mTc-PETS-L₁ and ^99mTc-DM-PETS. All four ^99mTc complexes exhibited similar brain, heart and pancreas extraction when injected into mice. These cummulative results imply that ^99mTc-PETS-L₁ and ^99mTc-DM-PETS are six-coordinated mononuclear ^99mTc(V) complexes and that ^99mTc-PETS-L₂ is a five-coordinated mononuclear ^99mTc(V) complex. These results also suggest that while the chelate ring structure of the ^99mTc-dithiosemicarbazone (DTS) chelate played a singificant role in its stability, ionization of the third proton of the PETS molecule and the subsequent resonating structure afforded further stability to the ^99mTc-PETS complex. Markedly high lipophilicity of the ^99mTc-PETS-L₂ may also be explained by assuming that ^99mTc-PETS-L₂ is the five-coordinated resonating structure.