This study investigates the effect of fractionated (two-part) PDT on the long-term local control rate (LCR) using the concentration of reactive oxygen species ([ROS]rx) as a dosimetry quantity. Groups with different fractionation schemes are examined, including a 2 h interval between light delivery sessions to cumulative fluences of 135, 180, and 225 J/cm2. While the total treatment time remains constant within each group, the division of treatment time between the first and second fractionations are explored to assess the impact on long-term survival at 90 days. In all preclinical studies, Photofrin is intravenously administered to mice at a concentration of 5 mg/kg, with an incubation period between 18 and 24 h before the first light delivery session. Fluence rate is fixed at 75 mW/cm2. Treatment ensues via a collimated laser beam, 1 cm in diameter, emitting light at 630 nm. Dosimetric quantities are assessed for all groups along with long-term (90 days) treatment outcomes. This study demonstrated a significant improvement in long-term survival after fractionated treatment schemes compared to single-fraction treatment, with the optimal 90-day survival increasing to 63%, 86%, and 100% vs. 20%, 25%, and 50%, respectively, for the three cumulative fluences. The threshold [ROS]rxfor the optimal scheme of fractionated Photofrin-mediated PDT, set at 0.78 mM, is significantly lower than that for the single-fraction PDT, at 1.08 mM.
本研究以活性氧浓度（[ROS]rx）作为剂量学参数，探讨分次（两次）光动力疗法对长期局部控制率的影响。研究比较了不同分次方案组，包括光照间隔2小时、累积能量密度分别为135、180和225 J/cm²的实验组。在保持各组总治疗时间恒定的前提下，通过调整首次与二次分次治疗的时间分配，评估其对90天长期生存率的影响。所有临床前研究中，小鼠经静脉注射浓度为5 mg/kg的卟吩姆钠，首次光照前孵育18至24小时。光照功率密度固定为75 mW/cm²，治疗采用直径1厘米的准直激光束，发射波长为630 nm。对各组进行剂量学参数测定及90天长期疗效评估。研究结果显示，与单次治疗相比，分次治疗方案能显著提升长期生存率：在三种累积能量密度下，最佳90天生存率分别提升至63%、86%和100%，而单次治疗组对应数据仅为20%、25%和50%。卟吩姆钠介导的分次光动力疗法最佳方案的[ROS]rx阈值为0.78 mM，显著低于单次治疗的阈值1.08 mM。
Fractionated Photofrin-Mediated Photodynamic Therapy Significantly Improves Long-Term Survival
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