IRRADIANCE AND PHOTOBLEACHING METRICS IN ALA PDT

ALA PDT 中的辐照度和光漂白指标

• 批准号: 6377960
• 负责人: ALLAN R OSEROFF
• 金额: $ 8.44万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6377960
• 关键词: basal cell carcinoma; clinical research; human subject; human therapy evaluation; neoplasm /cancer photoradiation therapy; photosensitizing agents; photostimulus

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.

局部ALA-PDT是一种很有前途的浅表癌治疗方法。然而，常规治疗可能导致光动力耗氧，限制了疗效。此外，还有明显的光照依赖性疼痛。治疗上的一个难题是，虽然低照射能最大限度地提高肿瘤内的氧气利用率，但也能显著延长治疗时间。由于PpIX的光漂白表现为氧依赖性，因此通过光敏剂荧光损失监测的光漂白率是光动力损伤的替代指标。高效的PDT具有较高的光漂白率。从皮肤吸收测量中获得的氧/脱氧血红蛋白比率，提供了光动力耗氧程度的独立测量，以及治疗期间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，皮肤温度的微小升高或降低可能对肿瘤和正常皮肤的血流以及PDT选择性产生显著影响。除了光漂白外，光照还会产生PpIX光产物以及其他可能具有不同吸收波长的内源性光敏剂。当光谱表征时，这些产物可以在PDT期间有效地激活。本初步研究的目的是使用荧光和反射率测量来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”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。在接受ALA-PDT治疗的浅表性基底细胞癌患者中，具体目的是：1。研究辐照度对PpIX初始光漂白（PB）率和pdt诱导疼痛的影响。2. 考察皮肤温度对光漂率、肿瘤选择性和不适的影响。3. 测定光产物或其他内源性光敏剂的辐照依赖性形成、血红蛋白氧合的变化和组织光学性质的变化。