Improvement of Tumor Response by Manipulation of Tumor Oxygenation During Photodynamic Therapy¶

Abstract

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.

Clinical system for interstitial photodynamic therapy with combined on-line dosimetry measurements

“…26 The lower limit for the tissue oxygenation for an effective treatment is an issue that has been debated in both PDT and radiotherapy. 7,38 Using the instrument reported here, this will be a question that we will address in future work. The calculation of the tissue oxygenation level as well as the derivation of changes in tissue optical properties that are consistent with the light transmission changes depend on the exact positioning of the fibers.…”

In vivo measurement of parameters of dosimetric importance during interstitial photodynamic therapy of thick skin tumors

“…12,14 Higher irradiances have been shown to lead to smaller treatment volumes, an effect that has been explained by oxygen depletion. 15,16 In addition, a good correlation has been found between the initial rate of sensitizer photobleaching and treatment outcome. 11,12,14 The kinetics of PPIX photobleaching has shown a fluence rate dependency, in that a higher irradiance leads to a less pronounced loss of fluorescence and lower initial photobleaching rate.…”

Regulation of miRNA Expression by Low-Level Laser Therapy (LLLT) and Photodynamic Therapy (PDT)

“…Another inherent consequence of PDT is local hypoxia, which can arise either directly, from oxygen consumption during treatment [105–107], or indirectly, from the destruction of tumor vasculature as a result of effective treatment [108,109]. Hypoxia is a major stimulus for angiogenesis, via its stabilization of the hypoxia-inducible factor-1α (HIF-1α) transcription factor [110,111].…”