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

Abstract

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.

Novel 99mTc ‘4 + 1’ peptide conjugates: Tuning the biodistribution by variation of coligands

“…These investigations confirm a suitable metabolic stability of the used cyclic RGD-peptide, the 99m Tc '4 þ 1' complex unit as also shown previously [2,11], and further of its novel versions grafted with the described pharmacokinetic modifiers.…”

Cell‐Specific and Nuclear Targeting with [M(CO)3]+ (M=99mTc, Re)‐Based Complexes Conjugated to Acridine Orange and Bombesin

“…[19] Thus, if the receptor-targeting molecule (a peptide for instance) is kept unchanged, the nucleus-targeting function can be altered without substantially varying the overall composition of the trifunctional conjugate. The isocyanide ligands 4 and 7 retained their nucleus-staining properties as could be seen in fluorescence microscopy studies with PC3 and B16F1 cells.…”

Myocardial uptake and biodistribution of newly designed technetium-labelled fatty acid analogues

“…The synthesis of the '3 + 1' and '4 + 1' mixed-ligand complexes has been published recently [11][12][13][14][15][16]. The preparation of the '3 + 1' 99m Tc complexes follows a onestep procedure as described before [13], with reduction of the pertechnetate with stannous(II) chloride, in the presence of the monodentate FA thiol and the tridentate ligand of choice, with propylene glycol as a co-solvent.…”

“…1b). These types of complex require the synthesis of o-isocyano-functionalized FAs [11,15]. Because of the instability of the free isonitrile-substituted acids, a conversion of the carboxylic acid group to a methyl ester function is necessary during the syntheses of ligand and complex.…”

“…1b). Since there is no oxygen on the technetium and the metal is well shielded by the ligand, this system is rather lipophilic and shows high stability towards challenging agents, e.g., an SH group containing biomolecules [11].…”