{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T09:13:17Z","timestamp":1773306797510,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,9,28]],"date-time":"2015-09-28T00:00:00Z","timestamp":1443398400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"JSPS KAKENHI","award":["26461901"],"award-info":[{"award-number":["26461901"]}]},{"name":"JSPS KAKENHI","award":["24390011"],"award-info":[{"award-number":["24390011"]}]},{"name":"the Platform for Drug Discovery, Informatics, and Structural Life Science from MEXT, Japan"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Magnetic Resonance in Med"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>The detailed in vivo T<jats:sub>1<\/jats:sub>\u2010weighted contrasting abilities of nitroxyl contrast agents, which have been used as redox responsive contrast agents in several magnetic resonance\u2010based imaging modalities, in mouse brain were investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Distribution and pharmacokinetics of five types of five\u2010membered\u2010ring nitroxyl radical compound were compared using T<jats:sub>1<\/jats:sub>\u2010weighted MRI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The blood\u2013brain barrier (BBB) \u2010impermeable 3\u2010carboxy\u20102,2,5,5\u2010tetramethylpyrrolidine\u2010<jats:italic>N<\/jats:italic>\u2010oxyl (CxP) could not be distributed in the brain. The slightly lipophilic 3\u2010carbamoyl\u20102,2,5,5\u2010tetramethylpyrrolidine\u2010<jats:italic>N<\/jats:italic>\u2010oxyl (CmP) showed slight distribution only in the ventricle, but not in the medulla and cortex. The amphiphilic 3\u2010methoxy\u2010carbonyl\u20102,2,5,5\u2010tetramethyl\u2010pyrrolidine\u2010<jats:italic>N<\/jats:italic>\u2010oxyl (MCP) had good initial uniform distribution in the brain and showed typical 2\u2010phase signal decay profiles. A brain\u2010seeking nitroxyl probe, acetoxymethyl\u20102,2,5,5\u2010tetramethyl\u2010pyrrolidine\u2010<jats:italic>N<\/jats:italic>\u2010oxyl\u20103\u2010carboxylate (CxP\u2010AM), showed an accumulating phase, and then its accumulation was maintained in the medulla and ventricle regions, but not in the cortex. The lipophilic 4\u2010(<jats:italic>N<\/jats:italic>\u2010methyl piperidine)\u22122,2,5,5\u2010tetramethylpyrroline\u2010<jats:italic>N<\/jats:italic>\u2010oxyl (23c) was well distributed in the cortex and medulla, but slightly in the ventricle, and showed relatively rapid linear signal decay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Nitroxyl contrast agents equipped with a suitable lipophilic substitution group could be BBB\u2010permeable functional contrast agents. MR redox imaging, which can estimate not only the redox characteristics but also the detailed distribution of the contrast agents, is a good candidate for a theranostic tool. 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