IRRADIANCE AND PHOTOBLEACHING METRICS IN ALA PDT

局部ALA-PDT是一种有前途的治疗浅表癌的方法。 然而，常规治疗可能导致光动力学氧耗尽，限制疗效。 此外，存在显著的辐射依赖性疼痛。 一个治疗难题是，虽然低辐照度最大限度地提高了癌细胞内的氧气利用率，但它们也可以显着延长治疗时间。由于PpIX的光漂白表现出氧依赖性，因此通过光敏剂荧光损失监测的光漂白速率是光动力损伤的替代度量。有效的PDT将具有高的光漂白速率。 从皮肤吸收测量获得的氧合/脱氧血红蛋白比率提供了光动力学氧消耗程度的独立测量以及关于治疗期间PDT诱导的灌注变化的信息。 皮肤灌注具有强烈的温度依赖性，皮肤温度的小幅升高或降低可能对癌组织和正常皮肤的血流以及PDT的选择性产生显著影响。 除了光漂白之外，光照还导致产生PpIX光产物和可能具有不同吸收波长的其他内源性光敏剂。 当光谱表征时，这些产物可以在PDT期间被有效地激活。这项试点研究的目标是使用荧光和反射率测量，以检查初始光漂白率作为辐照度和皮肤温度的函数。 我们试图定义一个“最佳”的初始光剂量率，提供足够的氧合，短的照明时间，和低PDT引起的疼痛。在用ALA-PDT治疗的浅表基底细胞癌患者中，具体目的/目标是：1.检查辐照度对初始PpIX光漂白（PB）速率和PDT诱导的疼痛的影响。 2.检查皮肤温度对光漂白速率、癌选择性和不适的影响。 3.确定光产物或其他内源性光敏剂的辐射依赖性形成，血红蛋白氧合的变化以及组织光学特性的改变。

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.