Experimental Study of Photoradiation Therapy by Argon pumped Dye Laser and Hematoporphyrin Derivative on Malignant Brain Tumor Model

Abstract

Photoradiation therapy (PRT) is a recently introduced treatment for malignant neoplasms which depends on tumor localization and retention of hematoporphyrin derivative (HpD) activated by a proper light in the presence of oxygen. The effect of PRT was investigated in vitro and in vivo using rat brain tumor (Tumor 9: T9) induced by N-methylnitrosourea. Argon-pumped dye laser at 630 nm was utilized to provide the activating beam. HpD (0, 5, 10, 50 μg/ml in concentration) was kept in contact with 5×105 T9 cells for 2 hours at 5% CO2, 37°C in dark. Then the cells were washed twice and laser irradiation using argon-pumped dye laser 50, 100, 150, and 200 mW in power was carried out. The treated cell death was determined by the dye exclusion method with trypan blue. A brain tumor model was developed by in vivo inoculation of 105-6 T9 cells in the right parietal lobe of Fisher 344 male rats. On day 14, 20 mg/kg of HpD was given intraperitoneally. On day 17, optical fiber from the laser was inserted stereotaxically through the previous burr hole with the same method as tumor inoculation, and PRT using laser 150 mW in power was carried out. Mean survival times of the PRT group, HpD alone group, laser alone group, and control group were compared. PRT effectively killed T9 cells in culture depending on HpD concentration and power of laser. The mean survival time of the control group and PRT group was 28.18±2.95 days (n=39) and 41.0±7.97 days (n=4), respectively (p<0.01). However, considerable brain edema was induced.