OXYGEN DIFFUSION AND REACTION-KINETICS IN THE PHOTODYNAMIC THERAPY OF MULTICELL TUMOR SPHEROIDS
OXYGEN DIFFUSION AND REACTION-KINETICS IN THE PHOTODYNAMIC THERAPY OF MULTICELL TUMOR SPHEROIDS
复制标题
DOI：
10.1088/0031-9155/39/12/003
复制
发表时间：
1994-12-01
影响因子：
3.5
通讯作者：
FOSTER, TH
中科院分区：
文献类型：
--
作者：
NICHOLS, MG;FOSTER, TH
在多细胞肿瘤球体模型的背景下，考虑了光动力治疗中氧扩散和反应动力学的影响。用Clark-style微电极（4 μ m直径尖端）进行的稳态氧测量使我们能够确定500 μ m直径EMT6/Ro球体的代谢耗氧量和氧扩散系数。这些值分别为5.77 μ mol l(-1) s（-1）和1460 μ mol m(2) s（-1）。利用随时间变化的电极测量方法，对激光辐照单个光致敏球体的氧浓度进行了拟合，得到了一对反应扩散方程的数值解。分析得出光动力耗氧率和光动力治疗氧敏感性的参数。这些实验导出的量用于计算在若干通量率照射期间球体内氧的时空分布和耗氧量。光动力耗氧量的空间分布强烈依赖于通量率。使用本报告中开发的实验和理论结果，分析先前发表的生存数据。分析表明，EMT6/Ro球体中单线态氧反应的阈值剂量为323 +/- 38 μ mol l(-1)（平均+/- SEM）。
Effects of oxygen diffusion and reaction kinetics in photodynamic therapy are considered in the context of a multicell tumour spheroid model. Steady-state measurements of oxygen made with a Clark-style microelectrode (4 mu m diameter tip) enable us to determine the rare of metabolic oxygen consumption and the oxygen diffusion coefficient in 500 mu m diameter EMT6/Ro spheroids. These values are 5.77 mu mol l(-1) s(-1) and 1460 mu m(2) s(-1), respectively. Time-dependent electrode measurements of oxygen concentration during laser irradiation of individual Photofrin(R)-sensitized spheroids are fitted to numerical solutions of a pair of diffusion-with-reaction equations. The analysis yields the rate of photodynamic oxygen consumption and a parameter that governs the oxygen sensitivity of photodynamic therapy. These experimentally derived quantities are used to calculate the temporal and spatial distributions of oxygen and the rate of oxygen consumption in a spheroid during irradiation at several fluence rates. The spatial distribution of photodynamic oxygen consumption is strongly fluence rate dependent. Using the experimental and theoretical results developed in this report, previously published survival data are analysed. The analysis indicates that the threshold dose of reacting singlet oxygen in the EMT6/Ro spheroid is 323 +/- 38 mu mol l(-1) (mean +/- SEM).