title: (2)H,(15)N-substituted nitroxides as sensitive probes for electron paramagnetic resonance imaging.
abstract: Electron paramagnetic resonance imaging (EPRI) using nitroxides is an emergent imaging method for studying in vivo physiology, including O(2) distribution in various tissues. Such imaging capabilities would allow O(2) mapping in tumors and in different brain regions following hypoxia or drug abuse. We have recently demonstrated that the anion of 3-carboxy-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl (2) can be entrapped in brain tissue to quantitate O(2) concentration in vivo. To increase the sensitivity of O(2) measurement by EPR imaging, we synthesized 3-carboxy-2,2,5,5-tetra((2)H(3))methyl-1-(3,4,4-(2)H(3),1-(15)N)pyrrolidinyloxyl (7). EPR spectroscopic measurements demonstrate that this fully isotopically substituted nitroxide markedly improves signal-to-noise ratio and, therefore, the sensitivity of EPR imaging. The new isotopically substituted nitroxide shows increased sensitivity to changes in O(2) concentration, which will enable more accurate O(2) measurement in tissues using EPRI.
authors.affiliation: Center for Biomedical Engineering and Technology, and Center for EPR Imaging In Vivo Physiology, University of Maryland, Baltimore, Maryland 21201, USA.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Burks
authors.forename: Justin
authors.initials: J
authors.lastname: Bakhshai
authors.forename: Mallory A
authors.initials: MA
authors.lastname: Makowsky
authors.forename: Sukumaran
authors.initials: S
authors.lastname: Muralidharan
authors.forename: Pei
authors.initials: P
authors.lastname: Tsai
authors.forename: Gerald M
authors.initials: GM
authors.lastname: Rosen
authors.forename: Joseph P Y
authors.initials: JP
authors.lastname: Kao
mesh_terms: D003903:Deuterium / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D015335:Molecular Probes / Q000737:chemistry*; D015394:Molecular Structure; D009587:Nitrogen Isotopes; D010100:Oxygen / Q000032:analysis; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: C488837:3-carboxy-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl; D015335:Molecular Probes; D009587:Nitrogen Isotopes; D011759:Pyrrolidines; D003903:Deuterium; D010100:Oxygen