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Low\u2010frequency electron paramagnetic resonance (EPR) spectroscopy with a paramagnetic probe is an attractive imaging modality that potentially can be used to map O<jats:sub>2<\/jats:sub> concentration in the brain. We examined two nitroxides, 3\u2010methoxycarbonyl\u20102,2,5,5\u2010tetramethyl\u20101\u2010pyrrolidinyloxyl [2] and 3\u2010acetoxymethoxycarbonyl\u20102,2,5,5\u2010tetramethyl\u20101\u2010pyrrolidinyloxyl [3], as pro\u2010imaging agents to deliver 3\u2010carboxy\u20102,2,5,5\u2010tetramethyl\u20101\u2010pyrrolidinyloxyl [1] across the blood\u2013brain barrier (BBB). In primary cultured neurons, nitroxide [3] but not [2] was hydrolyzed by intracellular esterases to [1], which, being anionic at physiologic pH, was well retained intracellularly. In contrast, [2] was not well retained by neurons. In vivo pharmacokinetic and pharmacodynamic studies in mice suggested that esterase\u2010labile nitroxide [3] crossed the BBB, and was converted to [1] and retained. Retention occurred in brain tissue and not in the extensive vasculature, as evidenced by the fact that removal of blood by whole\u2010body saline perfusion did not eliminate the nitroxide EPR signal from the brain. The EPR linewidths of [1] and [3] were more O<jats:sub>2<\/jats:sub>\u2010sensitive than that of the commonly\u2010used oximetry probe 4\u2010oxo\u20102,2,6,6\u2010tetramethylpiperidine\u2010d<jats:sub>16<\/jats:sub>\u20101\u2010<jats:sup>15<\/jats:sup>N\u2010oxyl [4]. Moreover, we used [3] in vivo to estimate O<jats:sub>2<\/jats:sub> concentration in mouse brains. These results indicate that nitroxide [3] could be useful for mapping O<jats:sub>2<\/jats:sub> distribution in the brain following stroke. Magn Reson Med, 2006. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/mrm.20894","type":"journal-article","created":{"date-parts":[[2006,5,5]],"date-time":"2006-05-05T16:05:43Z","timestamp":1146845143000},"page":"1433-1440","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Use of 3\u2010acetoxymethoxycarbonyl\u20102,2,5,5\u2010tetramethyl\u20101\u2010pyrrolidinyloxyl as an EPR oximetry probe: Potential for in vivo measurement of tissue oxygenation in mouse 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