Tirand Loraine, Bastogne Thierry, Bechet Denise, Linder Michel, Thomas Noémie, Frochot Céline, Guillemin François, Barberi-Heyob Muriel
Centre de Recherche en Automatique de Nancy, Nancy-University, CNRS, Centre Alexis Vautrin, Vandoeuvre-lès-Nancy, France.
Int J Radiat Oncol Biol Phys. 2009 Sep 1;75(1):244-52. doi: 10.1016/j.ijrobp.2009.04.004. Epub 2009 Jul 13.
Photodynamic therapy (PDT) is based on the interaction of a photosensitizing (PS) agent, light, and oxygen. Few new PS agents are being developed to the in vivo stage, partly because of the difficulty in finding the right treatment conditions. Response surface methodology, an empirical modeling approach based on data resulting from a set of designed experiments, was suggested as a rational solution with which to select in vivo PDT conditions by using a new peptide-conjugated PS targeting agent, neuropilin-1.
A Doehlert experimental design was selected to model effects and interactions of the PS dose, fluence, and fluence rate on the growth of U87 human malignant glioma cell xenografts in nude mice, using a fixed drug-light interval. All experimental results were computed by Nemrod-W software and Matlab.
Intrinsic diameter growth rate, a tumor growth parameter independent of the initial volume of the tumor, was selected as the response variable and was compared to tumor growth delay and relative tumor volumes. With only 13 experimental conditions tested, an optimal PDT condition was selected (PS agent dose, 2.80 mg/kg; fluence, 120 J/cm(2); fluence rate, 85 mW/cm(2)). Treatment of glioma-bearing mice with the peptide-conjugated PS agent, followed by the optimized PDT condition showed a statistically significant improvement in delaying tumor growth compared with animals who received the PDT with the nonconjugated PS agent.
Response surface methodology appears to be a useful experimental approach for rapid testing of different treatment conditions and determination of optimal values of PDT factors for any PS agent.
光动力疗法（PDT）基于光敏剂（PS）、光和氧之间的相互作用。很少有新的PS剂能发展到体内阶段，部分原因是难以找到合适的治疗条件。响应面法是一种基于一组设计实验数据的经验建模方法，被认为是一种合理的解决方案，可用于通过使用一种新的肽共轭PS靶向剂——神经纤毛蛋白-1来选择体内PDT条件。
选择Doehlert实验设计来模拟PS剂量、光通量和光通量率对裸鼠U87人恶性胶质瘤细胞异种移植瘤生长的影响及相互作用，采用固定的药物-光照间隔。所有实验结果均通过Nemrod-W软件和Matlab计算。
选择与肿瘤初始体积无关的肿瘤生长参数——内径生长率作为响应变量，并与肿瘤生长延迟和相对肿瘤体积进行比较。仅测试了13种实验条件，就选择了最佳的PDT条件（PS剂剂量为2.80mg/kg；光通量为120J/cm²；光通量率为85mW/cm²）。用肽共轭PS剂治疗荷胶质瘤小鼠，然后采用优化的PDT条件，与接受非共轭PS剂PDT的动物相比，在延迟肿瘤生长方面显示出统计学上的显著改善。
响应面法似乎是一种有用的实验方法，可用于快速测试不同的治疗条件，并确定任何PS剂的PDT因素的最佳值。
