Photodynamic therapy (
PDT) requires molecular
oxygen during light irradiation to generate
reactive oxygen species. Tumor hypoxia, either preexisting or induced by
PDT, can severely hamper the effectiveness of
PDT. 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 preexisting hypoxic cells. In this study hyperoxygenation 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 h later.
Tumor oxygenation was manipulated by subjecting the animals to 3
atp (atmospheric pressure) hyperbaric
oxygen or normobaric
oxygen during
PDT light irradiation. The results show a significant improvement in
tumor response when
PDT was delivered during hyperoxygenation. With hyperoxygenation up to 80% of treated
tumors showed no regrowth after 60 days. In comparison, when animals breathed room air, only 20% of treated
tumors did not regrow. To explore the effect of hyperoxygenation on
tumor oxygenation,
tumor partial
oxygen pressure was measured with
microelectrodes positioned in preexisting hypoxic regions before and during the
PDT. The results show that hyperoxygenation may oxygenate preexisting hypoxic cells and compensate for
oxygen depletion induced by
PDT light irradiation. In conclusion, hyperoxygenation may provide effective ways to improve
PDT efficiency by oxygenating both preexisting and treatment-induced cell hypoxia.