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Article: Use of 3-acetoxymethoxycarbonyl-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl as an EPR oximetry probe: Potential for in vivo measurement of tissue oxygenation in mouse brain

TitleUse of 3-acetoxymethoxycarbonyl-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl as an EPR oximetry probe: Potential for in vivo measurement of tissue oxygenation in mouse brain
Authors
Issue Date2006
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0740-3194/
Citation
Magnetic Resonance In Medicine, 2006, v. 55 n. 6, p. 1433-1440 How to Cite?
AbstractMeasurement of oxygen concentration and distribution in the brain is essential for understanding the pathophysiology of stroke. Low-frequency electron paramagnetic resonance (EPR) spectroscopy with a paramagnetic probe is an attractive imaging modality that potentially can be used to map O2 concentration in the brain. We examined two nitroxides, 3-methoxycarbonyl-2,2, 5,5-tetramethyl-1-pyrrolidinyloxyl [2] and 3-acetoxymethoxycarbonyl-2,2,5,5- tetramethyl-1-pyrrolidinyloxyl [3], as pro-imaging agents to deliver 3-carboxy-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl [1] across the blood-brain 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-labile 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-body saline perfusion did not eliminate the nitroxide EPR signal from the brain. The EPR linewidths of [1] and [3] were more O2-sensitive than that of the commonly-used oximetry probe 4-oxo-2,2,6,6-tetramethylpiperidine- d16-1-15Noxyl [4]. Moreover, we used [3] in vivo to estimate O2 concentration in mouse brains. These results indicate that nitroxide [3] could be useful for mapping O2 distribution in the brain following stroke. © 2006 Wiley-Liss, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/179435
ISSN
2015 Impact Factor: 3.782
2015 SCImago Journal Rankings: 2.197
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorShen, Jen_US
dc.contributor.authorLiu, Sen_US
dc.contributor.authorMiyake, Men_US
dc.contributor.authorLiu, Wen_US
dc.contributor.authorPritchard, Aen_US
dc.contributor.authorKao, JPYen_US
dc.contributor.authorRosen, GMen_US
dc.contributor.authorTong, Yen_US
dc.contributor.authorLiu, KJen_US
dc.date.accessioned2012-12-19T09:56:33Z-
dc.date.available2012-12-19T09:56:33Z-
dc.date.issued2006en_US
dc.identifier.citationMagnetic Resonance In Medicine, 2006, v. 55 n. 6, p. 1433-1440en_US
dc.identifier.issn0740-3194en_US
dc.identifier.urihttp://hdl.handle.net/10722/179435-
dc.description.abstractMeasurement of oxygen concentration and distribution in the brain is essential for understanding the pathophysiology of stroke. Low-frequency electron paramagnetic resonance (EPR) spectroscopy with a paramagnetic probe is an attractive imaging modality that potentially can be used to map O2 concentration in the brain. We examined two nitroxides, 3-methoxycarbonyl-2,2, 5,5-tetramethyl-1-pyrrolidinyloxyl [2] and 3-acetoxymethoxycarbonyl-2,2,5,5- tetramethyl-1-pyrrolidinyloxyl [3], as pro-imaging agents to deliver 3-carboxy-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl [1] across the blood-brain 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-labile 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-body saline perfusion did not eliminate the nitroxide EPR signal from the brain. The EPR linewidths of [1] and [3] were more O2-sensitive than that of the commonly-used oximetry probe 4-oxo-2,2,6,6-tetramethylpiperidine- d16-1-15Noxyl [4]. Moreover, we used [3] in vivo to estimate O2 concentration in mouse brains. These results indicate that nitroxide [3] could be useful for mapping O2 distribution in the brain following stroke. © 2006 Wiley-Liss, Inc.en_US
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0740-3194/en_US
dc.relation.ispartofMagnetic Resonance in Medicineen_US
dc.rightsMagnetic Resonance in Medicine. Copyright © John Wiley & Sons, Inc.-
dc.subject.meshAnimalsen_US
dc.subject.meshBrain - Metabolismen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshContrast Media - Pharmacokineticsen_US
dc.subject.meshElectron Spin Resonance Spectroscopy - Methodsen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Inbred C57blen_US
dc.subject.meshMolecular Probe Techniquesen_US
dc.subject.meshNeurons - Metabolismen_US
dc.subject.meshNitrogen Oxides - Diagnostic Use - Pharmacokineticsen_US
dc.subject.meshOximetry - Methodsen_US
dc.subject.meshOxygen Consumption - Physiologyen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Sprague-Dawleyen_US
dc.titleUse of 3-acetoxymethoxycarbonyl-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl as an EPR oximetry probe: Potential for in vivo measurement of tissue oxygenation in mouse brainen_US
dc.typeArticleen_US
dc.identifier.emailShen, J: shenjg@hku.hken_US
dc.identifier.emailTong, Y: tongyao@hku.hken_US
dc.identifier.authorityShen, J=rp00487en_US
dc.identifier.authorityTong, Y=rp00509en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1002/mrm.20894en_US
dc.identifier.pmid16680679-
dc.identifier.scopuseid_2-s2.0-33744951891en_US
dc.identifier.hkuros121742-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33744951891&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume55en_US
dc.identifier.issue6en_US
dc.identifier.spage1433en_US
dc.identifier.epage1440en_US
dc.identifier.isiWOS:000238051000024-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridShen, J=7404929947en_US
dc.identifier.scopusauthoridLiu, S=36094288000en_US
dc.identifier.scopusauthoridMiyake, M=7201843244en_US
dc.identifier.scopusauthoridLiu, W=7407343965en_US
dc.identifier.scopusauthoridPritchard, A=14008681800en_US
dc.identifier.scopusauthoridKao, JPY=7201375605en_US
dc.identifier.scopusauthoridRosen, GM=35497253700en_US
dc.identifier.scopusauthoridTong, Y=9045384000en_US
dc.identifier.scopusauthoridLiu, KJ=7404200456en_US

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