Oxorhenium and oxotechnetium [SNS/S] mixed ligand complexes having a pendant diisopropylaminoethyl-group. Synthesis, characterization and biodistribution studies

Abstract

A novel SNS tridentate ligand, the N,N-bis(2-mercaptoethyl)-N′,N′-diisopropylethylenediamine was synthesized and the corresponding oxorhenium and oxotechnetium “mixed ligand” complexes using 3 monodentate aromatic thiols as coligands were prepared and characterized. Rhenium complexes were obtained as crystals with high yield by substitution of ligand and coligand on the trichlorobis(triphenylphosphine)-rhenium(V) oxide using a molar ratio ligand:coligand:precursor of 1. Characterization was performed by HPLC analysis, UV-vis and IR spectra, elemental analysis and X-ray diffraction. Results were consistent with the ReOLC structure. The complexes adopted a distorted trigonal bipiramidal geometry and were neutral due to ionization of all sulphur atoms upon complexation. Consequently 99mTc complexes were also prepared and evaluated in mice as potential brain imaging agents. Labelling was performed by substitution using 99mTc-glucoheptonate as precursor. The labelling yield was over 85% and the radiochemical purity of the complexes over 99%. Biodistribution in mice demonstrated high uptake and retention in brain. However comparison with previously reported “mixed ligand” complexes showed that the incorporation of the diisopropylaminoethyl group in the SNS/S backbone is not enhancing the biological characteristics of this type of complexes. Copyright © 2000 John Wiley & Sons, Ltd.