IRRADIANCE AND PHOTOBLEACHING METRICS IN ALA PDT

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Topical ALA-PDT is a promising treatment for superficial carcinomas. However, conventional treatments probably cause photodynamic oxygen depletion, limiting efficacy. In addition, there is significant irradiance-dependent pain. A therapeutic dilemma is that while low irradiances maximize oxygen availability within the carcinomas, they also can significantly prolong treatment time. Because photobleaching of PpIX appears oxygen dependent, the photobleaching rate monitored by loss of photosensitizer fluorescence is a surrogate metric for photodynamic damage. Efficient PDT will have a high photobleaching rate. The oxy/deoxy hemoglobin ratio, obtained from skin absorption measurements, provides an independent measure of the extent of photodynamic oxygen depletion as well as information about PDT- induced perfusion changes during treatment. Cutaneous perfusion is strongly temperature dependent, and small increases or decreases in skin temperature may have significant effects on blood flow in carcinomas and in normal skin, and on PDT selectivity. In addition to photobleaching, illumination causes the production of PpIX photoproducts and possibly other endogenous photosensitizers with different absorption wavelengths. When spectrally characterized, these products may be usefully activated during PDT. The goals of this pilot study are to use fluorescence and reflectance measurements to examine the initial photobleaching rates as a function of irradiance and skin temperature. We seek to define an "optimum" initial light dose rate that provides adequate oxygenation, short illumination times, and low PDT- induced pain. In patients with superficial basal cell carcinomas treated with ALA-PDT, the Specific Aims/Objectives are to: 1. Examine the effect of irradiance on the initial PpIX photobleaching (PB) rate and PDT-induced pain. 2. Examine the effects of skin temperature on photobleaching rate, carcinoma selectivity and discomfort. 3. Determine the irradiance-dependent formation of photoproducts or other endogenous photosensitizers, the changes in hemoglobin oxygenation, and the alterations in tissue optical properties.