Mixed-Ligand Technetium(III) Complexes with Tetradendate/Monodendate NS3/Isocyanide Coordination:  A New Nonpolar Technetium Chelate System for the Design of Neutral and Lipophilic Complexes Stable in Vivo

• Published in: Bioconjugate chemistry Vol. 12; no. 4; pp. 538 - 544
• Main Authors: Pietzsch, H.-J, Gupta, A, Syhre, R, Leibnitz, P, Spies, H
• Format: Journal Article
• Language: English
• Published: American Chemical Society 18-07-2001
• ISSN: 1043-1802; 1520-4812
• DOI: 10.1021/bc0001591

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 the design of lipophilic 99mTc or 186Re/188Re radiopharmaceuticals.