Review of Tissue Oxygenation Sensing During Radiotherapy Based Upon Cherenkov-Excited Luminescence Imaging

Oxygen sensing with light has been developing for many decades using injectable molecules called Oxyphors, which are pegylated, dendrimer-encapsulated metalloporphyrins that have a phosphorescence emission lifetime that is a direct reporter of the local oxygen partial pressure (pO2). In recent years, the ability to image this emission from tissue with Cherenkov light excitation during high-energy X-ray-based radiation therapy has been shown and developed for research studies. The main value of this type of lifetime-based pO2 sensing, termed Cherenkov-Excited Luminescence Imaging (CELI) is in its ability to image values of pO2 from within the tissue during radiation therapy using tracers that are systemic and biologically compatible. Spatial mapping of pO2 can realized either as surface imaging or deep tissue tomography through a few centimeters. The spatial resolution is radiation dose-dependent but can be near 0.1 mm, based upon radiation doses expected in a fractionated treatment plan. When imaging tumors with a broad beam irradiation, histograms of pO2 values across the surface have been demonstrated illustrating microscopic sensitivity to the ranges of oxygen levels present, and the ability to track these microscopic histograms during daily fractionated radiation therapy is possible. The pO2 distributions provide for sensitivity to the hypoxic fraction of the tumor—a unique capability of oxygen imaging that has microscopic spatial sampling. Comparisons of the CELI pO2 method to other oxygen-sensing methods, as well as the ability to use the CELI technique as a tool to examine the optimization of radiation therapy treatment technique is ongoing.