Wang Hsing-Wen, Rickter Elizabeth, Yuan Min, Wileyto E Paul, Glatstein Eli, Yodh Arjun, Busch Theresa M
Department of Radiation Oncology, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Photochem Photobiol. 2007 Sep-Oct;83(5):1040-8. doi: 10.1111/j.1751-1097.2007.00139.x.
Photodynamic therapy (PDT) regimens that conserve tumor oxygenation are typically more efficacious, but require longer treatment times. This makes them clinically unfavorable. In this report, the inverse pairing of fluence rate and photosensitizer dose is investigated as a means of controlling oxygen depletion and benefiting therapeutic response to PDT under conditions of constant treatment time. Studies were performed for Photofrin-PDT of radiation-induced fibrosarcoma tumors over fluence rate and drug dose ranges of 25-225 mW cm(-2) and 2.5-10 mg kg(-1), respectively, for 30 min of treatment. Tumor response was similar among all inverse regimens tested, and, in general, tumor hemoglobin oxygen saturation (SO2) was well conserved during PDT, although the highest fluence rate regimen (225 mWx2.5 mg) did lead to a modest but significant reduction in SO2. Regardless, significant direct tumor cell kill (>1 log) was detected during 225 mWx2.5 mg PDT, and minimal normal tissue toxicity was found. PDT effect on tumor oxygenation was highly associated with tumor response at 225 mWx2.5 mg, as well as in all other regimens tested. These data suggest that high fluence rate PDT can be carried out under oxygen-conserving, efficacious conditions at low photosensitizer dose. Clinical confirmation and application of these results will be possible through use of minimally invasive oxygen and photosensitizer monitoring technologies, which are currently under development.
能保持肿瘤氧合状态的光动力疗法（PDT）方案通常疗效更佳，但所需治疗时间更长。这使其在临床上并不理想。在本报告中，研究了光通量率与光敏剂剂量的反向配对，作为在恒定治疗时间条件下控制氧消耗并有利于PDT治疗反应的一种方法。分别在光通量率为25 - 225 mW cm(-2)和药物剂量为2.5 - 10 mg kg(-1)的范围内，对辐射诱导的纤维肉瘤肿瘤进行了30分钟的Photofrin - PDT研究。在所有测试的反向方案中，肿瘤反应相似，并且一般来说，在PDT过程中肿瘤血红蛋白氧饱和度（SO2）得到了很好的保持，尽管最高光通量率方案（225 mWx².5 mg）确实导致SO2有适度但显著的降低。无论如何，在225 mWx².5 mg PDT期间检测到显著的直接肿瘤细胞杀伤（>1 log），并且发现正常组织毒性最小。在225 mWx².5 mg以及所有其他测试方案中，PDT对肿瘤氧合的影响与肿瘤反应高度相关。这些数据表明，高光通量率PDT可以在低光敏剂剂量且保持氧合的有效条件下进行。通过使用目前正在开发的微创氧和光敏剂监测技术，将有可能对这些结果进行临床验证和应用。
