title: Imaging thiol redox status in murine tumors in vivo with rapid-scan electron paramagnetic resonance.
abstract: Thiol redox status is an important physiologic parameter that affects the success or failure of cancer treatment. Rapid scan electron paramagnetic resonance (RS EPR) is a novel technique that has shown higher signal-to-noise ratio than conventional continuous-wave EPR in in vitro studies. Here we used RS EPR to acquire rapid three-dimensional images of the thiol redox status of tumors in living mice. This work presents, for the first time, in vivo RS EPR images of the kinetics of the reaction of2H,15N-substituted disulfide-linked dinitroxide (PxSSPx) spin probe with intracellular glutathione. The cleavage rate is proportional to the intracellular glutathione concentration. Feasibility was demonstrated in a FSa fibrosarcoma tumor model in C3H mice. Similar to other in vivo and cell model studies, decreasing intracellular glutathione concentration by treating mice with l-buthionine sulfoximine (BSO) markedly altered the kinetic images.
authors.affiliation: Center for EPR Imaging In Vivo Physiology, Department of Radiation and Cellular Oncology, University of Chicago, IL, USA.
authors.forename: Boris
authors.initials: B
authors.lastname: Epel
authors.affiliation: Center for EPR Imaging In Vivo Physiology, Department of Radiation and Cellular Oncology, University of Chicago, IL, USA.
authors.forename: Subramanian V
authors.initials: SV
authors.lastname: Sundramoorthy
authors.affiliation: Center for EPR Imaging In Vivo Physiology, Department of Radiation and Cellular Oncology, University of Chicago, IL, USA.
authors.forename: Martyna
authors.initials: M
authors.lastname: Krzykawska-Serda
authors.affiliation: Center for EPR Imaging In Vivo Physiology, Department of Radiation and Cellular Oncology, University of Chicago, IL, USA.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Maggio
authors.affiliation: Department of Biochemistry, School of Medicine, University of West Virginia, Morgantown, WV 26506, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Tseytlin
authors.affiliation: Department of Chemistry and Biochemistry, University of Denver, Denver, CO 80208, USA.
authors.forename: Gareth R
authors.initials: GR
authors.lastname: Eaton
authors.affiliation: Department of Chemistry and Biochemistry, University of Denver, Denver, CO 80208, USA.
authors.forename: Sandra S
authors.initials: SS
authors.lastname: Eaton
authors.affiliation: Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201, USA.
authors.forename: Gerald M
authors.initials: GM
authors.lastname: Rosen
authors.affiliation: Center for Biomedical Engineering & Technology, and Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Joseph P Y
authors.initials: JPY
authors.lastname: Kao
authors.affiliation: Center for EPR Imaging In Vivo Physiology, Department of Radiation and Cellular Oncology, University of Chicago, IL, USA. Electronic address: h-halpern@uchicago.edu.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Halpern
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000000981:diagnostic imaging*; D019328:Buthionine Sulfoximine / Q000737:chemistry; D003952:Diagnostic Imaging / Q000379:methods*; D004220:Disulfides / Q000737:chemistry; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D005260:Female; D005354:Fibrosarcoma / Q000000981:diagnostic imaging*; D005978:Glutathione / Q000378:metabolism; D021621:Imaging, Three-Dimensional; D007700:Kinetics; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism; D009589:Nitrogen Oxides / Q000737:chemistry; D010084:Oxidation-Reduction; D059629:Signal-To-Noise Ratio; D013113:Spin Labels / Q000138:chemical synthesis
chemical_list: D004220:Disulfides; D009589:Nitrogen Oxides; D013113:Spin Labels; D019328:Buthionine Sulfoximine; D005978:Glutathione
keywords: EPR imaging; Electron paramagnetic resonance; Glutathione; Rapid scan EPR; Thiol redox status