Simultaneous CW-EPR imaging of isotopic nitroxyl radicals

Introduction The distribution of enantiomers can be visualized with electron paramagnetic resonance (EPR) imaging if they are labeled with stable spin-probes such as nitroxyl radicals. To make in vivo imaging of chiral drugs possible, we first need to perform synthesis and toxicological studies for spin-labeled chiral drugs, as well as develop a simultaneous imaging method to visualize two enantiomers. A recent study showed that the anticancer drug Lomustin can be successfully labeled with a nitroxyl radical, without affecting its toxicological activity [1]. This study highlights the potential for the labeling of chiral molecules with isotopic nitroxyl radicals for the visualization of different EPR spectra. Three imaging methods based on magnetic resonance phenomena were reported for the simultaneous imaging of two or more kinds of free radicals: (i) spectral-spatial EPR imaging [2], (ii) Overhauser-enhanced magnetic resonance imaging [3] and (iii) EPR imaging based on a process of iterative deconvolution [4]. However, these methods are time-consuming and not suitable for three-dimensional (3D) imaging of short-lifetime radicals. As part of the development of in vivo imaging of chiral molecules, this study describes a method of simultaneous EPR imaging, which can visualize the spatial distributions of both Nand N-labeled nitroxyl radicals with no additional acquisition time.