Improvement of tumor response to photodynamic therapy by manipulation of tumor oxygenation in an in vivo model system

Photodynamic therapy (PDT) requires molecular oxygen during light irradiation in order to generate reactive oxygen species. Tumor hypoxia, either pre-existing or induced by PDT, can severely hamper the effectiveness of PDT treatment. Lowering the light irradiation dose rate or fractionating a light dose may improve cell kill of PDT induced hypoxic cells, but will have no effect on pre-existing hypoxic; cells. In this study, hyper-oxygenation technique was used during PDT to overcome hypoxia. C3H mice with transplanted mammary carcinoma tumors were injected with 12.5 mg/kg Photofrin and irradiated with 630 nm laser light 24 hours later. Tumor oxygenation was manipulated by subjecting the animals to 3 atp hyperbaric oxygen or normobanic oxygen during PDT light irradiation. The results show a significant improvement in tumor response when PDT was delivered during hyper-oxygenation. With hyper-oxygenation, up to 80% of treated tumors showed no re-growth after 60 days. hi comparison, only 20% of tumors treated while animals breathed room air did not re-grow. To explore the effect of hyperoxygenation on tumor oxygenation, tumor PO2 was measured with microelectrodes positioned in pre-existing hypoxic regions before and during the PDT. The results show that hyperoxygenation may oxygenate pre-existing hypoxic cells and compensate for oxygen depletion induced by PDT light irradiation. hi conclusion, hyper-oxygenation may provide effective ways to improve PDT treatment efficiency by oxygenating both pre-existing and treatment induced cell hypoxia.