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Differences in pharmacokinetic behaviors of two lipophilic 3‐substituted 2,2,5,5‐tetramethylpyrrolidine‐ N ‐oxyl radicals, in vivo probes to assess the redox status in the brain using magnetic resonance techniques
Author(s) -
Takeshita Keizo,
Okazaki Hana,
Tsukamoto Megumi,
Okazaki Shoko
Publication year - 2021
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.28499
Subject(s) - chemistry , radical , redox , in vivo , pharmacokinetics , reaction rate constant , hydroxymethyl , nuclear magnetic resonance , kinetics , stereochemistry , biochemistry , pharmacology , medicine , physics , microbiology and biotechnology , organic chemistry , quantum mechanics , biology
Purpose The pharmacokinetics of 3‐methoxycarbonyl‐ and 3‐hydroxymethyl‐2,2,5,5‐tetramethylpyrrolidine‐ N ‐oxyl radicals (MCP and HMP, respectively), magnetic resonance probes to assess the brain redox status, were examined in healthy mouse brains. Methods The time course of the concentration of the radical form of the probe in the brain was examined by signal enhancements on T 1 ‐weighted MR image after an intravenous injection. The distribution of the total probe (sum of radical and reduced forms) was investigated using brain homogenates. Results MCP distributed to the brain more than HMP. MCP exhibited biphasic decay with fast and slow components, whereas HMP exhibited monophasic decay with a similar rate constant to the slow component of MCP. Similar profiles were observed in various regions of the brain. The total probe for MCP exhibited monophasic decay at a similar rate constant to the slow component of the radical form; however, the initial content of the total probe was similar to its radical form. For HMP, decay of the total probe coincided with that of the radical form. Conclusion The decay of MCP needs to consider the reduction of the probe in and its elimination from the brain, while the decay of HMP may mainly result from its elimination from the brain.