CHARACTERIZATION OF TC-99M COMPLEXES OF PENTANE-2,4-DIONE BIS(N-METHYLTHIOSEMICARBAZONE)

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-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.