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- Title
Brain contrasting ability of blood-brain-barrier-permeable nitroxyl contrast agents for magnetic resonance redox imaging.
- Authors
Matsumoto, Ken‐ichiro; Yamasaki, Toshihide; Nakamura, Mizuki; Ishikawa, Junji; Ueno, Megumi; Nakanishi, Ikuo; Sekita, Aiko; Ozawa, Yoshikazu; Kamada, Tadashi; Aoki, Ichio; Yamada, Ken‐ichi
- Abstract
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. © 2015 Wiley Periodicals, Inc.
- Publication
Magnetic Resonance in Medicine, 2016, Vol 76, Issue 3, p935
- ISSN
0740-3194
- Publication type
Article
- DOI
10.1002/mrm.25918