Department of Radiation Oncology, School of Medicine, University of Pennsylvania Philadelphia, Pennsylvania 19104, USA.
Radiat Res. 2010 Sep;174(3):331-40. doi: 10.1667/RR2075.1.
Photodynamic therapy (PDT) with low light fluence rate has rarely been studied in protocols that use short drug-light intervals and thus deliver illumination while plasma concentrations of photosensitizer are high, creating a prominent vascular response. In this study, the effects of light fluence rate on PDT response were investigated using motexafin lutetium (10 mg/kg) in combination with 730 nm light and a 180-min drug-light interval. At 180 min, the plasma level of photosensitizer was 5.7 ng/microl compared to 3.1 ng/mg in RIF tumor, and PDT-mediated vascular effects were confirmed by a spasmodic decrease in blood flow during illumination. Light delivery at 25 mW/cm(2) significantly improved long-term tumor responses over that at 75 mW/cm(2). This effect could not be attributed to oxygen conservation at low fluence rate, because 25 mW/cm(2) PDT provided little benefit to tumor hemoglobin oxygen saturation. However, 25 mW/cm(2) PDT did prolong the duration of ischemic insult during illumination and was correspondingly associated with greater decreases in perfusion immediately after PDT, followed by smaller increases in total hemoglobin concentration in the hours after PDT. Increases in blood volume suggest blood pooling from suboptimal vascular damage; thus the smaller increases after 25 mW/cm(2) PDT provide evidence of more widespread vascular damage, which was accompanied by greater decreases in clonogenic survival. Further study of low fluence rate as a means to improve responses to PDT under conditions designed to predominantly damage vasculature is warranted.
低光强的光动力疗法（PDT）在那些使用短药物-光照间隔的方案中很少被研究，这些方案在光敏剂的血浆浓度高时进行照射，从而产生显著的血管反应。在这项研究中，使用莫替沙芬镥（10mg/kg）联合 730nm 光和 180 分钟的药物-光照间隔，研究了光强对 PDT 反应的影响。在 180 分钟时，与 RIF 肿瘤中的 3.1ng/mg 相比，光敏剂的血浆水平为 5.7ng/µl，并且在光照过程中血流的痉挛性减少证实了 PDT 介导的血管作用。以 25mW/cm2 的光传递显著改善了长期肿瘤反应，优于 75mW/cm2。这种效果不能归因于低光强下的氧气保存，因为 25mW/cm2 的 PDT 对肿瘤血红蛋白氧饱和度几乎没有益处。然而，25mW/cm2 的 PDT 确实延长了光照期间的缺血损伤持续时间，并且相应地与灌注的即刻下降更大相关，随后在 PDT 后几个小时内总血红蛋白浓度的增加较小。血液体积的增加表明从血管损伤不足引起的血液淤积；因此，25mW/cm2 的 PDT 后增加较小，提供了更广泛的血管损伤的证据，这伴随着集落形成存活的更大减少。进一步研究低光强作为一种在主要设计用于损伤血管的条件下改善 PDT 反应的方法是值得的。
