Direct and continuous measurements of oxygen partial pressure using a tissue-inserted optical oxygen microsensor: During photodynamic therapy

Photodynamic Therapy (PDT) is an anti-cancer treatment modality in which sensitizer drug, light and oxygen are used to photochemically cause cell death. The cytotoxicity of PDT is based on the toxic effects of singlet oxygen and other free radicals generated by the photosensitizer in target cells upon illumination. Successful application of anticancer therapy and especially PDT depends on oxygen content within the tumor. Application of an optical oxygen microsensor allowed continuous and direct in situ measurements of temporal variations in the oxygen partial pressure (1302) during PDT. The oxygen microsensor, developed by us in collaboration with OST, Israel, is an on-line system based on fluorescence measurements that provides continuous monitoring of blood and tissue oxygen levels. This study examined the spatial and temporal variations in the concentration of oxygen within solid tumors, during PDT. We found that illumination of Bacteriochlorophyll-Serine (a sensitizer drug) treated tumors leads to a rapid decline in tissue oxygen. Analysis of the process permitted a detailed description of the dynamics of oxygen depletion and reoxygenation. Moreover, it was shown that tumor oxygen tension becomes irreversibly low as a result of the effect of PDT. These results were interpreted in terms of vasculature damage. Magnetic resonance imaging studies confirmed the above findings and clearly showed that PDT induces vascular damage. Integration of the sensor in PDT experiments enables the in vivo analysis of the basic mechanisms underlying photoinduced cytotoxicity as well as the development of treatment protocols that optimize the synchronization of light pulses with tissue reoxygenation.