Brain contrasting ability of blood-brain-barrier–permeable nitroxyl contrast agents for magnetic resonance redox imaging

Ken Ichiro Matsumoto, Toshihide Yamasaki, Mizuki Nakamura, Junji Ishikawa, Megumi Ueno, Ikuo Nakanishi, Aiko Sekita, Yoshikazu Ozawa, Tadashi Kamada, Ichio Aoki, Ken Ichi Yamada

研究成果: Contribution to journalArticle査読

6 被引用数 (Scopus)


Purpose: The detailed in vivo T1-weighted contrasting abilities of nitroxyl contrast agents, which have been used as redox responsive contrast agents in several magnetic resonance-based imaging modalities, in mouse brain were investigated. Methods: Distribution and pharmacokinetics of five types of five-membered-ring nitroxyl radical compound were compared using T1-weighted MRI. Results: The blood–brain barrier (BBB) -impermeable 3-carboxy-2,2,5,5-tetramethylpyrrolidine-N-oxyl (CxP) could not be distributed in the brain. The slightly lipophilic 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-N-oxyl (CmP) showed slight distribution only in the ventricle, but not in the medulla and cortex. The amphiphilic 3-methoxy-carbonyl-2,2,5,5-tetramethyl-pyrrolidine-N-oxyl (MCP) had good initial uniform distribution in the brain and showed typical 2-phase signal decay profiles. A brain-seeking nitroxyl probe, acetoxymethyl-2,2,5,5-tetramethyl-pyrrolidine-N-oxyl-3-carboxylate (CxP-AM), showed an accumulating phase, and then its accumulation was maintained in the medulla and ventricle regions, but not in the cortex. The lipophilic 4-(N-methyl piperidine)−2,2,5,5-tetramethylpyrroline-N-oxyl (23c) was well distributed in the cortex and medulla, but slightly in the ventricle, and showed relatively rapid linear signal decay. Conclusion: Nitroxyl contrast agents equipped with a suitable lipophilic substitution group could be BBB-permeable functional contrast agents. MR redox imaging, which can estimate not only the redox characteristics but also the detailed distribution of the contrast agents, is a good candidate for a theranostic tool. Magn Reson Med 76:935–945, 2016.

ジャーナルMagnetic Resonance in Medicine
出版ステータス出版済み - 9 1 2016

All Science Journal Classification (ASJC) codes

  • 放射線学、核医学およびイメージング


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