A novel [99mTc≡N]2+ complex of metronidazole xanthate as a potential agent for targeting hypoxia

A xanthate derivative (L) at the pendant hydroxy group of metronidazole, a nitroimidazole known to possess affinity for hypoxic tumors, has been used as the carrier molecule for targeted delivery of the gamma-emitting radioisotope Tc-99m to tumors. The xanthate residues (S-2(-)) from two molecules of this ligand (L) were used for chelation with the [(TcN)-Tc-99m](2+) intermediate to form a square pyramidal and neutral [(TcN)-Tc-99m/L-2] complex in > 95% yield using a low ligand concentration of 1 mg/mL (similar to 3 x 10(-3) M). Biodistribution studies carried out in Swiss mice bearing fibrosarcoma tumor showed selective accumulation of the injected activity in the tumor (1.44 +/- 0.26% per gram 1 h pi) with major clearance through hepatobiliary route. The complex showed high tumor/muscle ratio (2.15 and 3.35 at 1 and 3 h post-injection, respectively) and tumor/blood ratio, which were comparable to hypoxia targeting agents Tc-99m-BMS181321 and Tc-99m-BRU59-21 reported earlier. (c) 2005 Elsevier Ltd. All rights reserved.