Fluoromisonidazole. A metabolic marker of myocyte hypoxia

Fluoromisonidazole is metabolically trapped in viable hypoxic cells in vitro. This property is the basis for the hypothesis that [¹⁸F]fluoromisonidazole can be used to detect hypoxic tissues noninvasively using positron emission tomography. To assess the potential usefulness of this compound as a marker for hypoxic myocardium, we measured the accumulation of [³H]fluoromisonidazole in isolated adult rat myocytes under normoxic, hypoxic (5,000 ppm O₂), and anoxic conditions. Both anoxia and hypoxia caused a marked increase in [³H[fluoromisonidazole accumulation. Relative to uptake during normoxia, uptake during anoxia was increased by 8.4-fold at 60 minutes and 26.5-fold at 180 minutes (p < 0.001). During hypoxia uptake was increased by 4.4-fold at 60 minutes and by 15.3-fold at 180 minutes (p < 0.001) and occurred in the absence of significant cell injury as measured by release of creatine kinase and changes in cell morphology. Additional studies demonstrated a slow oxygen-insensitive efflux of fluoromisonidazole or labeled metabolite(s) from myocytes reincubated in drug-free medium. We conclude that fluoromisonidazole is avidly retained in hypoxic myocytes and thus may be suitable for noninvasive detection of hypoxic myocardium using positron emission tomography.