Is misonidazole binding to mouse tissues a measure of cellular pO 2?

Abstract

Misonidazole (MISO), a hypoxic cell radiosensitizer, forms covalently-linked adducts to cellular molecules as a result of bioreductive metabolism, a process which is strongly dependent upon oxygen concentration. MISO binding to liver tissue taken from air-breathing mice was three to five times greater than binding to other normal tissues. The relative binding of [ 14C]MISO to various mouse tissue cubes in vitro was measured by autoradiography as a function of defined oxygen concentrations, and standard curves (binding rate vs oxygen concentration) were generated. The oxygen concentration for half-maximum binding as well as the maximum and minimum binding rates (grains per 100 μm 2) observed for liver tissue were not significantly different from those measured for brain or heart tissue. These results, along with previously published data on MISO binding to isolated hepatocytes in vitro, suggest that the elevated binding to liver in vivo may result, in part, from the organ existing at a significantly lower pO 2 than other normal tissues. They also suggest that this drug adduct procedure could be developed as a sensitive method for the quantitative measurement of tissue pO 2 at the cellular level.