Tc-III-based mixed complexes for the design and the development of new SPECT tracers

The trivalent state is the most stable oxidation state of technetium and rhenium, however, none of the radiopharmaceuticals currently in clinical use contains the metal in this oxidation state. We present here a general procedure for the preparation of a series of six-coordinated mixed ligand [99/99mTcIII(PS)2(Ln)] compounds, (PS = phosphino-thiolate; Ln = dithiocarbamate) to design a new class of TcIII-imaging agents. [99mTcIII(PS)2(Ln)] complexes were prepared in aqueous conditions, in high yield, by the addition of pertechnetate to a vial containing SnCl2 and the selected PS and Ln ligands. 99mTc-complexes were analyzed by HPLC and compared with the corresponding fully characterized 99Tc-complexes. All complexes are constituted by the [99/99mTcIII(PS)2]+ moiety where two phosphino-thiolate ligands are tightly bound to the metal while the remaining two positions are saturated by a dithiocarbamate chelate, also carrying bioactive molecules. All complexes were inert toward ligand exchange reactions. No significant in-vitro and in-vivo biotransformation were observed underlining their remarkable thermodynamic stability and kinetic inertness. These results can be utilized to design a novel class of 99mTcIII-based radiotracers useful for essential or target specific imaging agents. Acknowledgments This research was supported by MIUR (PRIN-20097FJHPZ-004 and FIRB-RBAP114AMK "RINAME") and by AIRC (IG-13121).