Whole-body kinetic image of a redox probe in mice using Overhauser-enhanced MRI

Nuttavut Kosem, Tatsuya Naganuma, Kazuhiro Ichikawa, Noppawan Phumala Morales, Keiji Yasukawa, Fuminori Hyodo, Ken Ichi Yamada, Hideo Utsumi

研究成果: ジャーナルへの寄稿学術誌査読

28 被引用数 (Scopus)

抄録

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, 50 mm), 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.

本文言語英語
ページ(範囲)328-336
ページ数9
ジャーナルFree Radical Biology and Medicine
53
2
DOI
出版ステータス出版済み - 7月 15 2012

!!!All Science Journal Classification (ASJC) codes

  • 生化学
  • 生理学(医学)

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