Monitoring of Singlet Oxygen Is Useful for Predicting the Photodynamic Effects in the Treatment for Experimental Glioma

Abstract

Singlet oxygen ((1)O(2)) generated in photodynamic therapy (PDT) plays a very important role in killing tumor cells. Using a new near-IR photomultiplier tube system, we monitored the real-time production of (1)O(2) during PDT and thus investigated the relationship between the (1)O(2) production and photodynamic effects. We did PDT in 9L gliosarcoma cells in vitro and in an experimental tumor model in vivo using 5-aminolevulinic acid and nanosecond-pulsed dye laser. During this time, we monitored (1)O(2) using this system. Moreover, based on the (1)O(2) monitoring, we set the different conditions of laser exposure and investigated whether they could affect the tumor cell death. We could observe the temporal changes of (1)O(2) production during PDT in detail. At a low fluence rate the (1)O(2) signal gradually decreased with a low peak, whereas at a high fluence rate it decreased immediately with a high peak. Consequently, the cumulative (1)O(2) at a low fluence rate was higher, which thus induced a strong photodynamic effect. The proportion of apoptosis to necrosis might therefore be dependent on the peak and duration of the (1)O(2) signal. A low fluence rate tended to induce apoptotic change, whereas a high fluence rate tended to induce necrotic change. The results of this study suggested that the monitoring of (1)O(2) enables us to predict the photodynamic effect, allowing us to select the optimal laser conditions for each patient.