In vivo visualization of redox status by high-resolution whole body magnetic resonance imaging using nitroxide radicals

Various diseases are known to be associated with an imbalance of the redox state, but in vivo detection of free radicals is difficult. The purpose of this study is to establish a method for in vivo visualization of redox status by high-resolution whole-body MRI using nitroxide radicals. A redox-sensitive nitroxide probe, 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (carbamoyl-PROXYL), was administered to rats intravenously, and in vivo T1-weighted MRI was performed to virtually visualize the redox status of various organs. In experiments using phantoms, a linear relationship between the MRI signal and the carbamoyl-PROXYL concentration persisted up to 80 mM. Among the phantoms, a sample containing 1 mM carbamoyl-PROXYL was readily identifiable. After intravenous injection of carbamoyl-PROXYL, whole-body T1-weighted MRI of the rat provided clear images with good spatial and temporal resolution. The signal intensities of four selected organs (heart, liver, kidney, and intestine) were analyzed quantitatively. The carbamoyl-PROXYL signal peaked and gradually declined due to reduction after intravenous injection. Among the four organs, the organ-specific reduction rate of carbamoyl-PROXYL was highest in the heart, followed by (in order) the liver, kidney, and intestine, and statistical analysis showed that the inter-organ differences were significant. In conclusion, T1-weighted carbamoyl-PROXYL-enhanced MRI provides excellent spatial and temporal imaging of carbamoyl-PROXYL distribution. Furthermore, it provides important functional information pertaining to blood flow and tissue redox activity in individual organs. MRI in combination with carbamoyl-PROXYL has potential clinical application for evaluation of redox activity in whole organs.