Hyperoxygenation Enhances the Tumor Cell Killing of Photofrin-mediated Photodynamic Therapy¶

Abstract

Tumor hypoxia, either preexisting or as a result of oxygen depletion during photodynamic therapy (PDT) light irradiation, can significantly reduce the effectiveness of PDT‐induced cell killing. To overcome tumor hypoxia and improve tumor cell killing, we propose using supplemental hyperoxygenation during Photofrin‐PDT. The mechanism for the tumor cure enhancement of the hyperoxygenation–PDT combination is investigated using an in vivo–in vitro technique. A hypoxic tumor model was established by implanting mammary adenocarcinoma in the hind legs of mice. Light irradiation (200 J/cm2 at either 75 or 150 mW/cm2), under various oxygen supplemental conditions (room air, carbogen, 100% normobaric or hyperbaric oxygen), was delivered to animals that received 12.5 mg/kg Photofrin 24 h before light irradiation. Tumors were harvested at various time points after PDT and grown in vitro for colony formation analysis. Treated tumors were also analyzed histologically. The results show that when PDT is combined with hyperoxygenation, the hypoxic condition could be improved and the cell killing rate at various time points after PDT could be significantly enhanced over that without hyperoxygenation, suggesting an enhanced direct and indirect cell killing associated with high‐concentration oxygen breathing. This study further confirms our earlier observation that when a PDT treatment is combined with hyperoxygenation it can be more effective in controlling hypoxic tumors.

Antitumor effects and blood flow dynamics after photodynamic therapy using benzoporphyrin derivative monoacid ring A in KLN205 and LM8 mouse tumor models

“…In this study, however, no significant difference in the delay in tumor regrowth was observed between the KLN205 and the LM8 tumors treated by the 3-h-interval PDT. These differences in the results of the in vitro and in vivo study might be due to the difference in the experimental condition and influence of several factors in the tumor tissue, such as photosensitizer uptake, tissue oxygen concentration, light dose delivered, etc [3,33,34].…”

A Review of Progress in Clinical Photodynamic Therapy

“…Nonetheless, the advent of newer photosensitizers and PDT technology has led to a renewed interest in evaluating intrapleural PDT (77). Hyperoxygenation is an effective means to enhance PDT cytotoxicity (78,79). Therefore, it is logical to carry out the intrapleural PDT under hyperbaric oxygenation (HBO) breathing to improve the therapeutic effect (80).…”

Synergistic interaction of 5-aminolevulinic acid-based photodynamic therapy with simultaneous hyperthermia in an osteosarcoma tumor model

“…Therefore, it is considered difficult to ensure the effectiveness of PDT in the deep area of a tumor due to local hypoxia. It has been reported that combination therapy with hyperbaric oxygen was effective to increase oxygen concentrations in the deep tissues of tumors and may enhance the effect of PDT (32,33). Furthermore, it has been estimated that increased blood flow of tumor vessels as a result of treatment may increase the oxygen supply and effectiveness of PDT.…”