EPR is making its way to clinical studies
Nowadays neurodegenerative disease such as Parkinson and Alzheimer’s are well known from taking their tolls. It is worth noticing that the imbalance between antioxidants and reactive oxygen species leads to damage caused by oxidative stress, and the oxidative damage is known for having an impact on the development of these diseases. The use of non-invasive EPR scanners and blood-brain permeative nitroxides, e.g. HMP or MCP, may be very helpful in the monitoring of changes in redox status.
The Japanese research group led by M.C Emoto, has carried out an examination of the distribution and time courses reduction of 3-hydroxymethyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (HMP) and 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-yloxy (MCP). Studies were presented in the paper “Dynamic changes in the distribution and time course of blood-brain barrier-permeative nitroxides in the mouse head with EPR imaging: visualization of blood flow in a mouse model of ischemia”.
The process of examination have consisted of several stages, which included the anatomical imaging of an animal by MRI, the injection of MCP and HMP into the mouse, and the non-invasive imaging of the brain by a 3D EPR tomograph. After the nitroxides were injected, the changes in redox state in brains of the mice were monitored. As a result, very significant conclusions have been reached. Co-registered imaging clearly pointed out the differences in localization of both nitroxides. HMP has been distributed uniformly in mouse head and, contrary to MCP, has not been accumulated within the brain. The difference has been also found in perfusion rate, for HMP seems to be slower.
After the in vivo studies, the mice were euthanized in order to assess the effect of blood flow on the redox reaction. Without blood flow, the half-life of HMP was significantly longer, while the half-life of MCP did not change at all. Nevertheless, MCP seems to be reduced inside the brain with no loss of MCP from the brain by washout.
It has been previously reported that many hydrophilic and lipophilic nitroxide compounds provide significant physiological information while being used as imaging probes. Designing of the experiment and the selection of the appropriate nitroxide spin probe can provide unique biological information, but it needs to be done with caution due to the lack of information about details concerning the time-dependent distribution and in vivo pharmacokinetics for the examination of small animals.
Emoto MC, Sato-Akaba, Hirata, Fujii HG; Dynamic changes in the distribution and time course of blood-brain barrier-permeative nitroxides in the mouse head with EPR imaging: visualization of blood flow in a mouse model of ischemia; Free Radic Biol Med. 2014 Sep;74:222-8; DOI: 10.1016/j.freeradbiomed.2014.06.026.