Wang Ken Kang-Hsin, Mitra Soumya, Foster Thomas H
Department of Physics and Astronomy, University of Rochester, Rochester, New York 14627, USA.
Med Phys. 2008 Aug;35(8):3518-26. doi: 10.1118/1.2952360.
Meso-tetra-hydroxyphenyl-chlorin (mTHPC, Foscan), a promising photosensitizer for photodynamic therapy (PDT), is approved in Europe for the palliative treatment of head and neck cancer. Based on work in mice that investigated optimal tumor accumulation, clinical protocols with Foscan typically employ an interval of 96 h between systemic sensitizer administration and irradiation. However, recent studies in mouse tumor models have demonstrated significantly improved long-term tumor response when irradiation is performed at shorter drug-light intervals of 3 and 6 h. Using a previously published theoretical model of microscopic PDT dosimetry and informed by experimentally determined photophysical properties and intratumor sensitizer concentrations and distributions, we calculated photodynamic dose depositions following mTHPC-PDT for drug-light intervals of 3, 6, 24, and 96 h. Our results demonstrate that the singlet oxygen dose to the tumor volume does not track even qualitatively with tumor responses for these four drug-light intervals. Further, microscopic analysis of simulated singlet oxygen deposition shows that in no case do any subpopulations of tumor cells receive a threshold dose. Indeed, under the conditions of these simulations more than 90% of the tumor volume receives a dose that is approximately 20-fold lower than the threshold dose for mTHPC. Thus, in this evaluation of mTHPC-PDT at various drug-light intervals, any PDT dose metric that is proportional to singlet oxygen creation and/or deposition would fail to predict the tumor response. In situations like this one, other reporters of biological response to therapy would be necessary.
中-四羟基苯基二氢卟吩（mTHPC，福斯卡林）是一种很有前景的用于光动力疗法（PDT）的光敏剂，在欧洲已被批准用于头颈部癌的姑息治疗。基于在小鼠身上研究最佳肿瘤蓄积情况的工作，福斯卡林的临床方案通常在全身给予敏化剂和照射之间采用96小时的间隔。然而，最近在小鼠肿瘤模型中的研究表明，当在3小时和6小时的较短药物-光照间隔下进行照射时，长期肿瘤反应有显著改善。利用先前发表的微观PDT剂量学理论模型，并根据实验确定的光物理性质、肿瘤内敏化剂浓度和分布，我们计算了mTHPC-PDT在3小时、6小时、24小时和96小时药物-光照间隔后的光动力剂量沉积。我们的结果表明，对于这四个药物-光照间隔，肿瘤体积的单线态氧剂量甚至在定性上都与肿瘤反应不相关。此外，对模拟单线态氧沉积的微观分析表明，在任何情况下肿瘤细胞的亚群都没有接受阈值剂量。实际上，在这些模拟条件下，超过90%的肿瘤体积接受的剂量比mTHPC的阈值剂量低约20倍。因此，在对mTHPC-PDT在不同药物-光照间隔下的评估中，任何与单线态氧产生和/或沉积成比例的PDT剂量指标都无法预测肿瘤反应。在这种情况下，需要其他治疗生物学反应的报告指标。
