OXYGEN DIFFUSION AND REACTION-KINETICS IN THE PHOTODYNAMIC THERAPY OFMULTICELL TUMOR SPHEROIDS

Effects of oxygen diffusion and reaction kinetics in photodynamic ther apy are considered in the context of a multicell tumour spheroid model . Steady-state measurements of oxygen made with a Clark-style microele ctrode (4 mu m diameter tip) enable us to determine the rare of metabo lic 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 measur ements 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 t he oxygen sensitivity of photodynamic therapy. These experimentally de rived quantities are used to calculate the temporal and spatial distri butions of oxygen and the rate of oxygen consumption in a spheroid dur ing irradiation at several fluence rates. The spatial distribution of photodynamic oxygen consumption is strongly fluence rate dependent. Us ing the experimental and theoretical results developed in this report, previously published survival data are analysed. The analysis indicat es that the threshold dose of reacting singlet oxygen in the EMT6/Ro s pheroid is 323 +/- 38 mu mol l(-1) (mean +/- SEM).