The objective of this work was to develop a novel (99m) Tc complex bearing the 5-nitroimidazol-1-yl moiety with recognised selectivity towards hypoxic tissue, as a potential radiopharmaceutical for imaging tumour hypoxia. The new metronidazole derivative (2-amine-3-[2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethylthio]propanoic acid) (L) containing adequate groups to coordinate technetium through the formation of a Tc(I)-tricarbonyl complex was synthesised with adequate yield (33%) and characterised by spectroscopy. Labelling was performed by substitution of three labile water molecules of the technetium tricarbonyl precursor, fac-[(99m)Tc(CO)3 (H2O)3](+) with the ligand. A radiochemical purity higher than 90% was achieved and remained unchanged for more than 4 h. The complex has a high stability in plasma, a moderate plasma protein binding and a moderate hydrophilicity. In vitro cell uptake studies showed a ratio between the activity taken up by cells in hypoxia/normoxia of 1.6 ± 0.4 (p < 0.5). Biodistribution in normal mice showed rapid depuration and low uptake in all organs and tissues except liver. Biodistribution in mice bearing induced tumours showed a low tumour uptake, but tumour/muscle ratio was favourable thanks to depuration. Comparison with biological results of other metronidazole derivatives clearly shows that modifications of the chelator are very important and contribute to improve the biological behaviour.
Keywords: 5-nitroimidazole derivatives; Tc-tricarbonyl complexes; hypoxia imaging agent.
Copyright © 2014 John Wiley & Sons, Ltd.