Synthesis and biological evaluation of a novel asymmetrical 99mTc-nitrido complex of metronidazole derivative

The novel dithiocarbamate derivative of metronidazole, potassium 2-(2-methyl-5-nitro-1H-imidazolyl)-ethyl-dithiocarbamate (MNIE-DTC), was synthesized as the pharmacophore-containing bifunctional ligand. The corresponding asymmetrical Tc-99m-nitrido complex, expected as a tumor hypoxia marker, had been successfully obtained by the addition of the biphosphine ligand PNP5 (PNP5 = N-ethoxethyl-NN-bis[2-(bis(3-methoxypropyl)phosphino) ethyl]-amine) and the dithiocarbamate ligand (MNIE-DTC) to the Tc-99m-nitrido precursor solution at 100 degrees 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 [(TcN)-Tc-99m(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 1 h), and the ratios of tumor/blood and tumor/muscle were 2.46 and 1.31 at 1 h p.i., and reached 4.52 and 2.86 at 4 h p.i., respectively. Copyright (C) 2007 John Wiley & Sons, Ltd.