title: Novel ascorbic acid-resistive nitroxide in a lipid emulsion: an efficient brain imaging contrast agent for MRI of small rodents.
abstract: Nitroxides have recently been used as redox-sensitive contrast agents for both MRI and EPR imaging. However, the rapid in vivo reduction in paramagnetism of nitroxides due to reductants such as ascorbic acid (AsA) has limited their use as contrast agents. This study developed a formulation of a newly synthesized AsA-resistive nitroxide (2,2,6,6-tetraethylpiperidine-4-one-1-oxyl (TEEPONE)) with a lipid emulsion system and examined the in vivo stability of TEEPONE by magnetic resonance imaging (MRI). MRI of mouse heads after administration of TEEPONE clearly indicated that TEEPONE has a remarkable in vivo stability and is a blood-brain barrier (BBB) permeable nitroxide. MRI also showed that TEEPONE is preferentially localized in the mouse brain. The distribution of TEEPONE in the mouse head can be controlled by the lipid content in the emulsion system used to solubilize TEEPONE.
authors: Center for Medical Education, Sapporo Medical University, Sapporo, Hokkaido 060-8556, Japan.
authors: Miho C
authors: MC
authors: Emoto
authors: Ken-Ichi
authors: K
authors: Yamada
authors: Mayumi
authors: M
authors: Yamato
authors: Hirotada G
authors: HG
authors: Fujii
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000737:chemistry; D001921:Brain / Q000033:anatomy & histology* / Q000378:metabolism*; D003287:Contrast Media / Q000138:chemical synthesis / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D004655:Emulsions / Q000737:chemistry*; D007089:Image Enhancement / Q000379:methods; D008055:Lipids / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000379:methods / Q000662:veterinary*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010880:Piperidines / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D012680:Sensitivity and Specificity; D012995:Solubility; D014018:Tissue Distribution
chemical_list: C570431:2,2,6,6-tetraethylpiperidine nitroxide; D003287:Contrast Media; D003497:Cyclic N-Oxides; D004655:Emulsions; D008055:Lipids; D010880:Piperidines; D001205:Ascorbic Acid