Photoradiation Therapy Causing Selective Tumor Kill in a Rat Glioma Model

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Abstract
We evaluated the effect of photoradiation therapy using the photosensitizer, hematoporphyrin derivative (HpD), and the argon-pumped rhodamine dye laser tuned to 630 nm in the rat C6glioma model. Animal models of cerebral glioma were established by implanting 106C6glioma cells in adult Wistar rats, and craniotomies were performed on normal and tumor-bearing animals. HpD in doses of up to 80 mg/kg followed by craniotomy resulted in no damage to the normal brain, and laser light at doses of up to 1200 joules/cm2without the prior administration of HpD produced no significant damage if the craniotomy site was irrigated with normal saline to prevent a temperature rise. Photoradiation caused no brain necrosis in non-tumor bearing animals if less than 20 mg of HpD per kg and 200 joules of red light per cm2were used. At higher doses of HpD and light, cerebral necrosis did occur. The depth of necrosis depended on the dose of both HpD and light. Treatment with 40 mg of HpD per kg and 400 joules of light per cm2resulted in cerebral necrosis in 50% of the treated animals. The mean depth of brain necrosis was 1.3 mm. Selective kill of a cerebral glioma with sparing of the normal brain was achieved with photoradiation therapy at doses of HpD of less than 20 mg/kg and light doses of less than 200 joules/cm2. At these doses, the mean depth of tumor kill was 4.5 mm. In 2 of 10 animals, the depth of tumor destruction was more than 6 mm. Increased tumor kill occurred at doses of HpD of 5 to 20 mg/kg, but increasing the dose of HpD above 20 mg/kg of body weight did not increase the depth of tumor destruction. There was a significantly greater depth of tumor kill if either 400 or 600 joules of red light per cm2was delivered compared with 200 joules of light per cm2in animals pretreated with either 20 or 40 mg of HpD per kg (P2or the dose of HpD above 20 mg/kg significantly increased the likelihood and extent of necrosis in normal brain. The depth of tumor destruction did not depend on the rate of delivery. The findings show that the dose of HpD and light is critical in achieving selective tumor kill, that the effective depth of kill is 4 to 7 mm, and that the tumor kill occurs independently of hyperthermia.