Irradiance: A parameter determining oxygenation during topical photodynamic therapy (PDT)
Becker, Theresa Louise
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PDT requires photosensitizer (PS), light and oxygen to generate the cytotoxic agent singlet oxygen ( 1 O 2 ). The topically applied pro-PSs aminolevulinic acid (ALA) and methyl 5-aminolevulinate (MAL), which lead to the endogenous production of the PS protoporphyrin IX (PpIX) by tumor cells, were investigated for the treatment of nonmelanoma skin cancers. Oxygen may become limited during treatment through various mechanisms, including changes in tumor perfusion hindering production of 1 O 2 and cell destruction. Treatment parameters that diminish oxygen limitation during PDT must be determined to optimize treatment effectiveness. PpIX within tumors and hypoxia was investigated. PpIX was found to be inhomogeneous in both mouse tumor models studied. Hypoxia was present at the start of treatment. PpIX was found to be distributed systemically in ALA applied animals but not in MAL applied animals. Photobleaching in both patients and mice was irradiance dependent, suggesting inadequate oxygenation at the higher irradiances. In the mice, photobleaching under anoxic conditions suggests diffusion of oxygen from the atmosphere is very important for the observed photobleaching. Blood flow was found to decrease in mice and increase in patients during topical PDT treatment. This was also dependent upon the irradiance used. The blood flow decrease in the mice was greatest at the highest irradiance of 75 mW/cm 2 . In the patients, the blood flow increase was least at the highest irradiance of 150 mW/cm 2 .