Synthesis and biological evaluation of a novel asymmetrical 99m Tc‐nitrido complex of metronidazole derivative

The novel dithiocarbamate derivative of metronidazole, potassium 2‐(2‐methyl‐5‐nitro‐1 H ‐imidazolyl)‐ethyl‐dithiocarbamate (MNIE‐DTC), was synthesized as the pharmacophore‐containing bifunctional ligand. The corresponding asymmetrical 99m Tc‐nitrido complex, expected as a tumor hypoxia marker, had been successfully obtained by the addition of the biphosphine ligand PNP5 (PNP5 = N ‐ethoxethyl‐ N , N ‐bis[2‐(bis(3‐methoxypropyl)phosphino)ethyl]‐amine) and the dithiocarbamate ligand (MNIE‐DTC) to the 99m Tc‐nitrido precursor solution at 100°C for 15 min. The radiochemical purity of the product was above 95% as measured by thin‐layer chromatography and high‐performance liquid chromatography. In vitro studies showed that the complex possessed good stability under physiological conditions. Its partition coefficient studies indicated that it was a lipophilic complex. The electrophoresis results showed that the complex was cationic. Biological evaluation of the complex [ 99m TcN(PNP5)(MNIE‐DTC)] + performed in Kunming mice bearing H22 tumor showed that the complex had a moderate tumor uptake (0.57±0.06%ID/g at 1h), and the ratios of tumor/blood and tumor/muscle were 2.46 and 1.31 at 1h p.i., and reached 4.52 and 2.86 at 4h p.i., respectively. Copyright © 2007 John Wiley & Sons, Ltd.