Jesus Pacheco-Torres1,2, Paloma Ballesteros2, Pilar Lopez-Larrubia1, Sebastian Cerdan1
1Biomedical Research Institute "Alberto Sols" - CSIC/UAM, Madrid, Spain; 2Laboratory of Organic Synthesis & Molecular Imaging, UNED, Madrid, Spain
Nitroimidazolyl derivatives (Pimonidazole, Misonidazole, EF5) have been traditionally used by different imaging methods as markers for hypoxia due to their preferential reduction and subsequent trapping in vivo under hypoxic conditions. However, these results remained difficult to interpret since the reduction mechanism and its rate determining steps remained largely unexplored. We address here the latter two aspects. We show that it is the intracellular redox state (NADP/NADPH, GSSG/GSH), rather than the oxygen tension, what determines the reduction rate of these compounds, the rection rate being limited mainly by the GSH concentration. This is a general mechanism occurring in all nitromidazolyl derivatives investigated.