Differential clearance of nitroxide MRI contrast agents from rat cerebral ventricles

Seven stable nitroxides have been evaluated as contrast agents in MRI studies of the rat cerebroventricular system. Because the contrast enhancement is primarily confined to the cerebral ventricles, nitroxides can be used to examine the ventricular structure. On the other hand, based on the absence of reducing agents in the rat CSF and on the fact that nitroxides can be reduced intracellularly, the relative reduction in contrast subsequent to an intracerebral injection provides information on the relationship of chemical structure to transmembrane flux in vivo. Observed rate constants and rate constants due to reduction have been analyzed quantitatively by modeling the effects of flow with GdDTPA, which is not subject to reduction. Five-membered ring nitroxides, in general, were reduced at much slower rates than six-membered ring nitroxides. The presence of a positive charge in the structure can substantially slow down the transmembrane flux.