Mixed-ligand technetium(III) complexes with tetra-dendate/monodendate NS₃/isocyanide coordination: A new nonpolar Technetium chelate system for the design of neutral and lipophilic complexes stable in vivo

Starting from the tripodal ligand 2,2',2"-nitrilotris(ethanethiol) (NS₃) and isocyanides (CNR) as co-ligands neutral mixed-ligand technetium(III) complexes of the general formulation [Tc(NS₃)(CNR)] have been synthesized and characterized. The ⁹⁹Tc complexes can be obtained by a two-step reduction/substitution procedure starting from [TcO₄]^- via the phosphine-containing precursor complex [Tc(NS₃)(PMe₂Ph)]. As shown by X-ray structural analyses the complexes adopt a nearly ideal trigonal-bipyramidal geometry with the trigonal plane formed by the three thiolate sulfurs of the tripodal ligand. The central nitrogen atom of the chelate ligand and the monodendate isocyanides occupy the apical positions.
The no-carrier-added preparation of the corresponding ^99mTc complexes was performed by a one-step procedure starting from ^99m[TcO₄]^- with stannous chloride as reducing agent.
Biodistribution studies in the rat demonstrated for the nonpolar, lipophilic compounds a significant initial brain uptake. In vitro challenge experiments with glutathione clearly indicated that no transchelation reaction occurs. Furthermore, there were no indications for reoxidation of Tc(III) to Tc(V) species or pertechnetate. We propose this type of complexes as a useful tool in designing of lipophilic ^99mTc or ¹⁸⁶Re/¹⁸⁸Re radiopharmaceuticals.