Synthesis and characterization of a {ReO}3+ complex with S- and N-donor ligands and of its 99m Tc analog

Abstract

A novel mixed-ligand 99mTc complex with mercaptobenzothiazole (mer) as ligand and aminothiazole (amino) as coligand was prepared and evaluated as potential brain radiopharmaceutical. Preparation at tracer level was accomplished by substitution, using 99mTc-gluconate as precursor and a coligand/ligand ratio of 5. Under these conditions, the labeling yield was over 97% and the major product with radiochemical purity >97% was isolated by HPLC and used for biological evaluation. The reaction of [ReO(Citrate)2]− with mer and amino in hot MeOH yields [ReO(mer)(amino)OH(H2O)2]. The DFT study demonstrated that the complex contains distorted octahedral ReO(V). The Re coordination sphere consists of the terminal oxo group, the S donor atom of the deprotonated mer, the N atom of the deprotonated amino, OH group, and two water molecules. Biodistribution in mice demonstrated early brain uptake, fast blood clearance, and excretion through hepatobiliary system. Although the brain/blood ratio increased significantly with time, the novel 99mTc complex did not exhibit ideal properties as brain perfusion radiopharmaceutical since brain uptake was too low.