Synthesis, characterization and biological evaluation of a novel "3+1" mixed ligand Tc-99m complex having an aliphatic thiol as coligand

A novel "3 + 1" mixed ligand Tc-99m complex with N,N-bis(2-mercaptoethyl)-N 'N'-diethyl-ethilenediamine as ligand and 1-octanethiol as coligand was pre pared and evaluated as potential brain radiopharmaceutical. Preparation at tracer level was accomplished by substitution, using Tc-99m-glucoheptonate as precursor and a coligand/ligand ratio of 5. Under these conditions the l abeling yield was over 80% and a major product with radiochemical purity >8 0% was isolated by HPLC methods and used for biological evaluation. Chemica l characterization at carrier level was developed using the corresponding r henium and Tc-99g complexes. Results were consistent with the expected "3 1" structure and X-ray diffraction study demonstrated that the complex ado pted a distorted trigonal bipyramidal geometry. All sulphur atoms underwent ionization leading to the formation of a neutral compound. Biodistribution in mice demonstrated early brain uptake, fast blood clearance and excretio n through hepatobiliary system. Although brain/blood ratio increased signif icantly with time, this novel Tc-99m complex did not exhibit ideal properti es as brain perfusion radiopharmaceutical since brain uptake was too low. ( C) 2001 Elsevier Science Ltd. All rights reserved.