A novel approach to robust Tc(III) Mixed-ligand chelates as tools for conjugating biologically active molecules

To date most Tc compounds suitable for coupling to biologically active molecules, e.g. CNS receptor targeted agents, are square-pyramidal complexes of the oxo ion [Tc=O]³⁺. However, the properties and thus the in vivo behaviour of such complexes are strongly influenced by the quite polar Tc=O unit offering a free position trans to the oxo ligand for further reaction in vivo. The stricter the requirements for specific agents, the more important is the question whether such a polarity is beneficial or not. Alternatives are oxo-free lower oxidation states. Here we report on prototypic trigonal-bipyramidal mixed-ligand complexes 1, 2 and 3 which are neutral, non-polar and robust since they contain sterically well shielded oxo-free Tc(III). We describe the syntheses and structural analyses of ⁹⁹Tc complexes with simple co-ligands serving as models for functionalized derivatives, the no-carrier-added preparation of the analogous ^99mTc-complexes as well as their stability in aqueous solution and in plasma, and their biodistribution in rats.