TY - JOUR
T1 - A novel ascorbic acid-resistant nitroxide in fat emulsion is an efficient brain imaging probe for in vivo EPR imaging of mouse
AU - Emoto, Miho
AU - Mito, Fumiya
AU - Yamasaki, Toshihide
AU - Yamada, Ken Ichi
AU - Sato-Akaba, Hideo
AU - Hirata, Hiroshi
AU - Fujii, Hirotada
N1 - Funding Information:
The authors report no conflicts of interest. The authors alone are responsible for the content and writing the paper.The work was supported by a grant from the Japan Society for the Promotion of Science (19390322 to HF) and SENTAN, JST. HH was supported by NEXT program (LR002), Japan Society for the promotion of Science.
PY - 2011/11
Y1 - 2011/11
N2 - 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.
AB - 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.
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U2 - 10.3109/10715762.2011.618499
DO - 10.3109/10715762.2011.618499
M3 - Article
C2 - 21888561
AN - SCOPUS:80555127477
VL - 45
SP - 1325
EP - 1332
JO - Free Radical Research
JF - Free Radical Research
SN - 1071-5762
IS - 11-12
ER -