Does in vivo oxidation of Hypoxyprobe (pimonidazole) compromise its effectiveness as a hypoxia marker?
The piperidine moiety in pimonidazole is easily oxidized to its N-oxide metabolite that, in principle, could impact the effectiveness of pimonidazole as a hypoxia marker. (See Arteel et al for a detailed discussion of the metabolism underlying the use of pimonidazole as a hypoxia marker (1)). Pimonidazole N-oxide is formed in vivo via the action of flavin mono-oxygenases (FMO). FMO isoform distribution varies among species producing different plasma levels of N-oxide (2, 3) although the route of pimonidazole administration has little impact on plasma levels of N-oxide (2). Hydrogen peroxide (4) and other, strong oxidants such as peroxynitrate formed by the reaction of superoxide anion with nitrous oxide (NO) can oxidize pimonidazole raising the possibility that pimonidazole N-oxide is produced in regions of fluctuating hypoxia in tumor and normal tissue. Although pimonidazole N-oxide can be formed by a number of mechanisms in vivo, there is reason to believe that this does not compromi
