title: A novel ascorbic acid-resistant nitroxide in fat emulsion is an efficient brain imaging probe for in vivo EPR imaging of mouse.
abstract: The loss of paramagnetism of nitroxide radicals due to reductant reactions in biological systems, places a fundamental time constraint on their application as an imaging probe in in vivo EPR imaging studies. However, in vitro studies of the newly synthesized tetraethyl-substituted piperidine nitroxide radical demonstrated high resistivity to paramagnetic reduction when exposed to ascorbic acid, a common reduction agent in biological systems. In this work we investigated the use of these nitroxides as an imaging probe in EPR imaging of small rodents. 2,2,6,6-Tetraethyl-piperidine nitroxide (TEEPONE) is not highly soluble in aqueous media, thus a lipid-based emulsion system of lecithin was used to solubilize TEEPONE. The obtained solution was homogenous and with low viscosity, allowing smooth intravenous injection into mice tail vein. Acquired three dimensional (3D) EPR images of mouse head clearly showed TEEPONE distributed in all tissues including brain tissues, with an average measurable signal half-life of more than 80 min, thus demonstrating high resistivity to reduction due to ascorbic acid in in vivo animal studies, and the potential for use of this compound in in vivo studies of animal model systems.
authors: Center for Medical Education, Sapporo Medical University, Sapporo, Hokkaido, Japan.
authors: Miho
authors: M
authors: Emoto
authors: Fumiya
authors: F
authors: Mito
authors: Toshihide
authors: T
authors: Yamasaki
authors: Ken-Ichi
authors: K
authors: Yamada
authors: Hideo
authors: H
authors: Sato-Akaba
authors: Hiroshi
authors: H
authors: Hirata
authors: Hirotada
authors: H
authors: Fujii
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000737:chemistry*; D001921:Brain / Q000033:anatomy & histology*; D003497:Cyclic N-Oxides / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D005217:Fat Emulsions, Intravenous / Q000737:chemistry; D006257:Head; D054709:Lecithins / Q000737:chemistry; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010880:Piperidines / Q000737:chemistry*; D012995:Solubility; D013113:Spin Labels
chemical_list: C570431:2,2,6,6-tetraethylpiperidine nitroxide; D003497:Cyclic N-Oxides; D005217:Fat Emulsions, Intravenous; D054709:Lecithins; D010880:Piperidines; D013113:Spin Labels; D001205:Ascorbic Acid