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 enh ancement is primarily confined to the cerebral ventricles, nitroxides can be used to examine the ventricular structure. On the other hand, b ased 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 informa tion on the relationship of chemical structure to transmembrane flux i n vivo. Observed rate constants and rate constants due to reduction ha ve been analyzed quantitatively by modeling the effects of flow with G dDTPA, which is not subject to reduction. Five-membered ring nitroxide s, in general, were reduced at much slower rates than six-membered rin g nitroxides. The presence of a positive charge in the structure can s ubstantially slow down the transmembrane flux.