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

A novel mixed-ligand ^99m Tc 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 ^99m Tc-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 ^99m Tc complex did not exhibit ideal properties as brain perfusion radiopharmaceutical since brain uptake was too low.