IRRADIANCE AND PHOTOBLEACHING METRICS IN ALA PDT

ALA PDT 中的辐照度和光漂白指标

• 批准号: 6158333
• 负责人: ALLAN R OSEROFF
• 金额: $ 8.34万
• 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 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6158333
• 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是治疗浅表性癌的一种有前途的治疗方法。然而，常规治疗可能会导致光动力耗氧，从而限制疗效。此外，还有明显的辐射依赖性疼痛。一个治疗难题是，虽然低辐射能最大限度地提高癌症内的氧气利用率，但它们也可以显著延长治疗时间。由于PPIX的光漂白表现为氧依赖，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指标。高效的PDT将具有较高的光漂白速率。从皮肤吸收测量获得的氧合/脱氧血红蛋白比率，提供了光动力耗氧程度的独立测量以及治疗过程中PDT诱导的血流变化的信息。皮肤血流灌注强烈依赖于温度，皮肤温度的微小升高或降低可能会对肿瘤和正常皮肤的血流量以及PDT选择性产生显著影响。除了光漂白，光照还会导致产生PpIX光产物，可能还会产生其他吸收波长不同的内源性光敏剂。当光谱表征时，这些产物可能在光动力疗法期间被有效地激活。这项初步研究的目标是使用荧光和反射率测量来检查初始光漂白速度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，以提供足够的氧气、较短的光照时间和较低的PDT诱导的疼痛。ALA-PDT治疗浅表性基底细胞癌的具体目的是：1.检测照射对PpIX初始光漂白(PB)率和PDT诱导的疼痛的影响。2.研究皮肤温度对光漂白率、肿瘤选择性和不适感的影响。3.确定光产物或其他内源性光敏剂的照度依赖性形成，血红蛋白氧合的变化，以及组织光学性质的变化。