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

Abstract

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 99mTc to tumors. The xanthate residues (S 2 −) from two molecules of this ligand (L) were used for chelation with the [ 99mTcN] 2+ intermediate to form a square pyramidal and neutral [ 99mTcN/L 2] complex in >95% yield using a low ligand concentration of 1 mg/mL (∼3 × 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 99mTc-BMS181321 and 99mTc-BRU59-21 reported earlier.