title: Whole-body kinetic image of a redox probe in mice using Overhauser-enhanced MRI.
abstract: Overhauser-enhanced MRI (OMRI) enables visualization of free radicals in animals based on dynamic nuclear polarization. Real-time data of tissue redox status gathered from kinetic images of redox-sensitive nitroxyl radical probes using OMRI provided both anatomic and physiological information. Phantom experiments demonstrated the linear correlation between the enhancement factor and the concentration of a membrane-impermeable probe, carboxy-PROXYL (3-carboxy-2,2,5,5-tetramethyl- pyrrolidine-1-oxyl). Whole-body OMRI images illustrated the in vivo kinetics of carboxy-PROXYL for 25 min. Initial distribution was observed in lung, heart, liver, and kidney, but not brain, corresponding to its minimal lipophilicity. Based on these images (pixel size, 1.33 × 1.33 mm; slice thickness, 50mm), a time-concentration curve with low coefficient of variance (<0.21) was created to assess pharmacokinetic behaviors. A biexponential curve showed a distribution phase from 1 to 10 min and an elimination phase from 15 to 25 min. The α rate constant was greater than the β rate constant in ROIs, confirming that its pharmacokinetics obeyed a two-compartment model. As a noninvasive technique, combining OMRI imaging with redox probes to monitor tissue redox status may be useful in acquiring valuable information regarding organ function for preclinical and clinical studies of oxidative diseases.
authors.affiliation: Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Nuttavut
authors.initials: N
authors.lastname: Kosem
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Naganuma
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ichikawa
authors.forename: Noppawan
authors.initials: N
authors.lastname: Phumala Morales
authors.forename: Keiji
authors.initials: K
authors.lastname: Yasukawa
authors.forename: Fuminori
authors.initials: F
authors.lastname: Hyodo
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Yamada
authors.forename: Hideo
authors.initials: H
authors.lastname: Utsumi
mesh_terms: D000818:Animals; D003497:Cyclic N-Oxides / Q000493:pharmacokinetics*; D005260:Female; D007091:Image Processing, Computer-Assisted; D007700:Kinetics; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods; D051379:Mice; D015335:Molecular Probes / Q000493:pharmacokinetics*; D009589:Nitrogen Oxides / Q000032:analysis*; D010084:Oxidation-Reduction; D019047:Phantoms, Imaging; D011759:Pyrrolidines / Q000493:pharmacokinetics*; D013113:Spin Labels; D013997:Time Factors
chemical_list: C499782:3-carboxy-2,2,5,5-tetramethylpyrrolidin-1-yloxyl; D003497:Cyclic N-Oxides; D015335:Molecular Probes; D009589:Nitrogen Oxides; D011759:Pyrrolidines; D013113:Spin Labels; C039900:nitroxyl