Oxygen-dependent metabolism of potential magnetic resonance contrast agents

Contrast agents have been investigated in an effort to increase the differences between the proton relaxation times of normal and pathologic tissue, and thus improve the ability to detect regions of pathology. Data on the oxygen-dependent metabolism of three nitroxides that are potential MRI contrast agents are presented. The amount of active, paramagnetic nitroxide remaining in suspensions of mammalian cells was followed as a function of time using electron-spin resonance spectroscopy. Data on the rates of nitroxide reduction over a wide range of oxygen concentrations are presented and show these rates as a function of the intracellular oxygen concentration. When intracellular oxygen concentrations were measured, only cells that were severely hypoxic reduced these potential contrast agents at increased rates. Because regions of some types of pathology are often hypoxic, the oxygen-dependent metabolism of nitroxides should allow contrast to be achieved on the basis of differences in metabolism between normal and diseased tissues. Further, the data suggest that future studies of nitroxide metabolism need to take into account the O2 concentration in order to understand the observed reduction rates and to predict the rates under other conditions.