Non-invasive measurement and visualization of free radicals in vivo would be important to clarify their roles in the pathogenesis of free radical-associated diseases. Nitroxyl radicals can react with free radicals and be derivatized to achieve specific cellular / subcellular localizing capabilities while retaining the simple spectral features useful in imaging. Overhauser-enhanced magnetic resonance imaging (OMRI), which is a double resonance technique, creates images of free radical distributions in small animals by enhancing the water proton signal intensity via the Overhauser Effect. In this study, we synthesized various nitroxyl probes having 15N nuclei and deuterium, and measured the enhancement factor for Overhauser-enhanced magnetic resonance imaging experiments. 15N-D-4- Oxo-2,2,6,6-tetramethylpiperidine-1-oxyl (15N-D-oxo-TEMPO) has the highest enhancement factor compared with other nitroxyl probes. The proton signal enhancement was higher for 15N-labeled nitroxyl probes when compared to the 14N-labeled analogues because of the reduced spectral multiplicity of the I = 1/2 nucleus. Furthermore, this enhancement is proportional to the line width and number of electron spin resonance lines of nitroxyl radicals. Finally, we compared the Overhauser-enhanced magnetic resonance image of 15N-labeled, deuterated 4-Oxo-2,2,6,6- tetramethylpiperidine-1-oxyl with that of 14N-H-TEMPOL. These results suggested that the selective deuteration of the nitroxyl probes enhanced the signal-to-noise ratio and thereby improved spatial and temporal resolutions.
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