Monitoring of singlet oxygen is useful for predicting the photodynamic effects in the treatment for experimental glioma

Purpose: Singlet oxygen (O-1(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 O-1(2) during PDT and thus investigated the relationship between the O-1(2) production and photodynamic effects. Experimental Design: 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 O-1(2) using this system. Moreover, based on the O-1(2) monitoring, we set the different conditions of laser exposure and investigated whether they could affect the tumor cell death. Results: We could observe the temporal changes of O-1(2) production during PDT in detail. At a low fluence rate the O-1(2) signal gradually decreased with a low peak, whereas at a high fluence rate it decreased immediately with a high peak. Consequently, the cumulative O-1(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 O-1(2) signal. A low fluence rate tended to induce apoptotic change, whereas a high fluence rate tended to induce necrotic change. Conclusions:The results of this study suggested that the monitoring of O-1(2) enables us to predict the photodynamic effect, allowing us to select the optimal laser conditions for each patient.