Biological evaluation and SPECT imaging of tumor hypoxia using a novel technetium-99m labeled tracer with 2-nitroimidazole moiety

To develop novel Tc-99m labeled nitroimidazole imaging agents for imaging tumor hypoxia, Tc-99m labeled ethylene diamine tetraacetic acid derivative of 4-nitroimidazole was reported by us earlier, which showed disadvantage of an unsatisfactory tumor-to-blood ratio. Therefore, 2-nitroimidazole was adopted as a pharmacophore to synthesize EDTA-2-EtNHNM, which was radiolabeled with Tc-99m in high yield to achieve Tc-99m-EDTA-2-EtNHNM. Tc-99m-EDTA-2-EtNHNM was hydrophilic and exhibited good in vitro stability. Cellular experiment demonstrated its hypoxic selectivity while biodistribution results showed improved tumor-to-blood and tumor-to-muscle ratios. SPECT imaging studies of Tc-99m-EDTA-2-EtNHNM indicated obvious accumulation in tumor, suggesting its potential to be a radiotracer for imaging tumor hypoxia.