Abstract
Purpose: Photodynamic therapy (PDT) induced singlet oxygen (1O2) can cause rapid necrosis of solid tumors. Using a new near-infrared photomultiplier tube system, the 1O2 production was monitored in real-time for HSC-3 tongue cancer cells and in vivo tissue, and the relationship between the 1O2 production and anti-tumor effects was investigated.
Experimental Design: Using 5-aminolevulinic acid (5-ALA), 1O2 generation was induced with a variety of laser parameters (fluence and irradiation) in vivo. During this time, tumor death was evaluated. Based on the 1O2 production, the optimal irradiation conditions and the long-term outcome were investigated on a subcutaneous tongue cancer model over 90 days.
Methods and Results: The 1O2 production showed a strong correlation with the laser output in a dose-dependent manner. At high laser output, the 1O2 levels were high and caused gradual but strong anti-tumor effects, whereas at low laser outputs, the 1O2 levels were low and the anti-tumor effects were rapid but superficial. We then performed PDT in an experimental tongue cancer model at an irradiance lower than 150 mW/cm2, which was identified in the first part of the study as the optimal irradiance value based on the 1O2 production. Within the 90 days post PDT, PDT-induced hemorrhagic necrosis was observed in 8 mice out of 10 within 5 days. In the other 2 mice, no sign of necrosis was seen until 25 days after PDT. The tumor volume of the PDT group continued to decline except for 2 mice which showed some slight growth over 70 days after PDT. In the control group, tumor size increased dramatically over 70 days.
Conclusions: The present studies established 1O2 levels as an indicator for optimal irradiation during PDT, and showed a relationship between the 1O2 production and the photodynamic effects. Although 5-ALA mediated PDT showed a strong anti-tumor effect on larger subcutaneous tongue tumors, it might be more effective for small tumors of oral cavity.
