Dynamic Monitoringof the Partial Pressure of Oxygenand pH in a Human Monocytic Cell Culture System Using Rapid-Scan ElectronParamagnetic Resonance Imaging with a Monophosphonated Trityl SpinProbe

Tissue pH and oxygenation are fundamental determinants of cellular metabolism, enzyme activity, and cell survival, and their dysregulation is a hallmark of many pathophysiological processes and diseases including cancer. Concurrent multiparametric mapping of the partial pressure of oxygen (pO2) and pH in a tumor model provides more biologically informative insights. However, such a mapping technique needs to be explored in potentially applicable imaging modalities. This article presents the proof of concept for dynamic concurrent monitoring of pO2 and pH using rapid-scan electron paramagnetic resonance (RS-EPR) and a monophosphonated triarylmethyl radical, HOPE spin probe. A home-built 800-MHz RS-EPR spectrometer/imager was used for four-dimensional spectral-spatial EPR imaging. The time-resolved mapping of pO2 and pH was demonstrated for a human monocyte cell culture system over 7 h. Temporal shifts in pO2 and pH were detected in the three-dimensional parametric data. From these results, it was shown that dynamic concurrent monitoring of pO2 and pH is feasible using RS-EPR and a monophosphonated trityl radical probe.