Imaging of reactive oxygen species generated in vivo.

Purpose: We sought to image the biodistribution of reactive oxygen species (ROS) within the living body using an in vivo electron spin resonance (ESR) imaging system using a spin probe, 1-acetoxy-3-carbamoyl-2,2,5,5-tetramethylpyrroline (ACP) that produces ESR-detectable nitroxide upon reaction with ROS.

Methods: Acute hepatic injury was induced in mice by priming with heat-killed Corynebacterium parvum followed by injection of a low dose of lipopolysaccharide. ACP was administered intravenously and an in vivo ESR imaging system was used to visualize hepatic oxidative stress.

Results: In this immune-mediated hepatic injury model, significant oxidative stress was evident at 3 h after lipopolysaccharide administration before the onset of massive hepatic injury. ACP was administered intravenously at 3 h after lipopolysaccharide injection when significant hepatic oxidative stress had been observed, and the ESR imaging system detected a high signal for 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine (carbamoyl-PROXYL), which had originated from the ACP-derived hydroxylamine and produced large amount of ROS within the living body. Using the ESR imaging system with ACP, we were able to visualize ROS in the abdomen before onset of hepatic injury.

Conclusion: We have succeeded in visualizing ROS within the body before onset of organ damage, representing a significant development in imaging for toxic molecules.