Hexadentate technetium-99m bis(thiosemicarbazonato) complexes: synthesis, characterisation and biodistribution

The syntheses of non-oxido/non-nitrido bis(thiosemicarbazonato)technetium(V) complexes featuring a series of alkyl and ether substituents is presented. The bis(thiosemicarbazones) were radiolabelled with technetium-99m using an optimised one-pot synthesis from [^99mTc][TcO₄]^-. Mass spectrometry and computational chemistry data suggested a distorted trigonal prismatic coordination environment for the bis(thiosemicarbazonato)technetium(V) complexes by way of a bis(thiosemicarbazone)technetium(V)-oxido intermediate complex. The lipophilicities of the complexes were estimated using distribution ratios and three of the new complexes were investigated in mice using kinetic planar imaging and ex vivo biodistribution experiments and were compared to [^99mTc][TcO₄]^-. Modification of the technetium complexes with various lipophilic functional groups altered the biodistributions of the complexes in mice despite evidence suggesting limited stability of the complexes to biologically relevant conditions. The most hydrophilic complex had higher uptake in the kidneys compared to the most lipophilic, which had higher liver uptake, suggesting modification of the excretion pathways.