Magnetic resonance imaging of organic contrast agents in mice: capturing the whole-body redox landscape
Magnetic resonance imaging of organic contrast agents in mice: capturing the whole-body redox landscape
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DOI：
10.1016/j.freeradbiomed.2010.11.028
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发表时间：
2011-02-01
影响因子：
7.4
通讯作者：
Mitchell, James B.
中科院分区：
文献类型：
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作者：
Davis, Ryan M.;Matsumoto, Shingo;Mitchell, James B.
氮氧化物是一类稳定的自由基，具有多种生物医学应用，包括辐射防护和组织氧化还原状态的非侵入性评估。对于这两种应用，有必要了解氮氧化物在体内的生物分布和还原。在这项研究中，核磁共振成像被用来比较两个通常研究的氮氧化物：哌啶氮氧化物坦普尔和吡咯烷氮氧化物3-CP的组织蓄积(浓度)和还原。研究发现，在体内，3-CP的还原速度比坦普尔慢3-11倍(取决于组织)，最大组织浓度因组织而异(0.6-7.2 mM)。对于给定的组织，两种氮氧化物的最大浓度通常不会改变。此外，利用电子顺磁共振光谱，我们发现氮氧化物的还原速率仅在体内预期的氧气范围内弱依赖于细胞内的Po(2)。这些观察结果与组织间观察到的氮氧化物还原速率的显著差异相结合，表明组织Po(2)不是体内氮氧化物还原速率的主要决定因素。对于氧化还原成像的目的，3-CP被证明是基于体内观察到的可实现的浓度和生物还原的最佳选择。由爱思唯尔公司出版。
Nitroxides are a class of stable free radicals that have several biomedical applications including radioprotection and noninvasive assessment of tissue redox status. For both of these applications, it is necessary to understand the in vivo biodistribution and reduction of nitroxides. In this study, magnetic resonance imaging was used to compare tissue accumulation (concentration) and reduction of two commonly studied nitroxides: the piperidine nitroxide Tempol and the pyrrolidine nitroxide 3-CP. It was found that 3-CP was reduced 3 to 11 times slower (depending on the tissue) than Tempol in vivo and that maximum tissue concentration varies substantially between tissues (0.6-7.2 mM). For a given tissue, the maximum concentration usually did not vary between the two nitroxides. Furthermore, using electron paramagnetic resonance spectroscopy, we showed that the nitroxide reduction rate depends only weakly on cellular pO(2) in the oxygen range expected in vivo. These observations, taken with the marked variation in nitroxide reduction rates observed between tissues, suggest that tissue pO(2) is not a major determinant of the nitroxide reduction rate in vivo. For the purpose of redox imaging, 3-CP was shown to be an optimal choice based on the achievable concentrations and bioreduction observed in vivo. Published by Elsevier Inc.