2H,15N-Substituted Nitroxides as Sensitive Probes for Electron Paramagnetic Resonance Imaging

Electron paramagnetic resonance imaging (EPRI) using nitroxides is an emergent imaging method for studying in vivo physiology, including O-2 distribution in various tissues. Such imaging capabilities would allow O-2 mapping in tumors and in different brain regions following hypoxia or drug abuse. We have recently demonstrated that the anion of 3-carboxy-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl (2) can be entrapped in brain tissue to quantitate O-2 concentration in vivo. To increase the sensitivity of O-2 measurement by EPR imaging, we synthesized 3-carboxy-2,2,5,5-tetra(H-2(3))methyl-1-(3,4,4-H-2(3),1-N-15)pyrrolidinyloxyl (7). EPR spectroscopic measurements demonstrate that this fully isotopically substituted nitroxide markedly improves signal-to-noise ratio and, therefore, the sensitivity of EPR imaging. The new isotopically substituted nitroxide shows increased sensitivity to changes in O-2 concentration, which will enable more accurate O-2 measurement in tissues using EPRI.