Use of 2-nitroimidazoles as bioreductive markers for tumour hypoxia

Tumour hypoxia is thought to contribute to some failures of radiotherapy to achieve local control. Polarographic measurements of tumour oxygenation ha ve been shown to predict clinical response to radiotherapy and patient surv ival. Hypoxia is also involved in many common types of normal tissue morbid ity. However, at present there is no widely used method of measuring hypoxi a in the clinic, or for individualizing therapy on the basis of tumour or t issue oxygenation. The bioreductive metabolism of 2-nitroimidazoles provide s a way of labelling hypoxic cells in vivo and a variety of isotopic labels have been proposed for the non-invasive detection of bound metabolites of these markers. Several 2-nitroimidazoles with immunologically identifiable side-chains have been described and conventional immunostaining procedures can be used to locate their metabolites, bound to hypoxic cells in histolog ical sections. Use of fluorescent immunoreagents allows flow cytometric ass essment of hypoxia and multiple colour fluorescent staining allows hypoxia to be correlated with other markers on a cell by cell basis. 2-Nitroimidazo le hypoxia markers show considerable promise for clinical use in diagnosing hypoxia and their use could allow rational application of hypoxia-related therapies to those patients most likely to benefit from them.