Invited Symposium: Photodynamic Therapy
Photodynamic therapy (PDT) requires tissue oxygenation during light irradiation. Tumor hypoxia, either pre-existing or induced by PDT during light irradiation , can severely hamper the effectiveness of a PDT treatment. Lowering light irradiation dose rate or fractionating a light dose may improve cell kills of PDT induced hypoxic cells, but will have no effects on pre-existing hypoxic cells. In the current study, we used hyper-oxygenation during PDT to overcome cell hypoxia in PDT.
Materials and Methods
C3H mice with transplanted mammalian carcinoma tumor on legs were injected with 12.5 mg/kg Photofrin irradiated 24 hours prior light treatment. To manipulate tumor oxygenation, the animals were subjected to 100% O2 in an enclosed chamber at either normobaric or 3 atmospheric pressure. The tumors were irradiated with 630 nm laser during the hyper-oxygenation inside the chamber. Various light delivery rate was tested as listed below. To further distinguish the mechanisms how hyper-oxygenation manipulates tumor oxygenation, clamps/rubber band were used to stop blood flow into the tumor during a PDT treatment. Tumor responses to various hyper-oxygenation schemes have been investigated in following experimental groups:
We also measured tumor oxygenation. An oxygen microelectrode was inserted into tumor hypoxic region and tissue pO2 was continuously recorded in all phases of a PDT/Hyper-oxygenation treatment.
Results and Discussion:Fig. 1:"Tumor oxygenation during PDT/Hyper-oxygenation treatment"
Figure 1 shows a typical dynamic changes of tumor pO2 during a PDT/Hyper-oxygenation treatment. Note that the oxygen electrode is linearly calibrated between 0-50 mmHg. We have confirmed that tumor oxygenation can be directly manipulated by subjecting tumor bearing animals to various hyper-oxygenation conditions. When animals are treated in either normo- or hyperbaric oxygen chamber, their tumor oxygen level in previous hypoxic region can be improved significantly. PDT treatment can reduce tumor pO2 level, but not to diminish it.fig. 2:Tumor responses
The results from leg tumors treated with 200J/cm2 (bolded groups above) are summarized in Figure 2. It clearly shows that hyper-oxygenation enhances tumor response to a PDT treatment. In specific:
Discussion and Conclusion
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|Chen, Q; Hetzel, FW; (1998). Photodynamic Therapy (PDT) with Simultaneous Hyper-oxygenation. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/rainbow/chen0820/index.html|
|© 1998 Author(s) Hold Copyright|