Mixed-ligand technetium(III) complexes with tetradendate/monodendate NS(3)/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) (NS(3)) and isocyanides (CNR) as co-ligands, neutral mixed-ligand technetium(III) complexes of the general formulation [Tc(NS(3))(CNR)] have been synthesized and characterized. The (99)Tc complexes can be( )()obtaine...

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Bibliographic Details
Published in:Bioconjugate chemistry 2001-07, Vol.12 (4), p.538-544
Main Authors: Pietzsch, H J, Gupta, A, Syhre, R, Leibnitz, P, Spies, H
Format: Article
Language:English
Subjects:
Animals
Brain - metabolism
Chelating Agents - chemistry
Crystallography, X-Ray
Cyanides - chemical synthesis
Drug Design
Drug Stability
Glutathione - chemistry
Liver - metabolism
Male
Organotechnetium Compounds - chemical synthesis
Oxidation-Reduction
Phosphines - chemical synthesis
Rats
Rats, Wistar
Technetium - blood
Technetium - chemistry
Technetium - pharmacokinetics
Tissue Distribution
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Summary:Starting from the tripodal ligand 2,2',2' '-nitrilotris(ethanethiol) (NS(3)) and isocyanides (CNR) as co-ligands, neutral mixed-ligand technetium(III) complexes of the general formulation [Tc(NS(3))(CNR)] have been synthesized and characterized. The (99)Tc complexes can be( )()obtained by a two-step reduction/substitution procedure starting from [TcO(4)](-) via the phosphine-containing precursor complex [Tc(NS(3))(PMe(2)Ph)]. 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 (99m)Tc complexes was performed by a one-step procedure starting from (99m)[TcO(4)](-) 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 (99m)Tc or (186)Re/(188)Re radiopharmaceuticals.
ISSN:1043-1802