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

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)935-945
Number of pages11
JournalMagnetic Resonance in Medicine
Volume76
Issue number3
DOIs
Publication statusPublished - Sep 1 2016

All Science Journal Classification (ASJC) codes

  • Radiology Nuclear Medicine and imaging

Fingerprint Dive into the research topics of 'Brain contrasting ability of blood-brain-barrier–permeable nitroxyl contrast agents for magnetic resonance redox imaging'. Together they form a unique fingerprint.

Cite this