Mitra Soumya, Foster Thomas H
Department of Radiology, University of Rochester, 601 Elmwood Avenue, Box 648, Rochester, NY 14642, USA.
Photochem Photobiol. 2005 Jul-Aug;81(4):849-59. doi: 10.1562/2005-02-22-RA-447.
Meso-tetra-hydroxyphenyl-chlorin (mTHPC) is one of the most potent photosensitizers currently available for clinical photodynamic therapy (PDT). However the reason or reasons for its high photodynamic efficacy remain(s) unresolved. To investigate the PDT efficacy of mTHPC vs Photofrin we use the knowledge of photophysical parameters extracted from the analysis of oxygen electrode measurements in spheroids to compute and compare their respective singlet oxygen (1O2) dose depositions. The electrode measurements indirectly report the bleaching kinetics of mTHPC and indicate that its photobleaching mechanism is consistent with 1O2-mediated reactions. mTHPC's photodegradation via 1O2 reactions is confirmed by a more direct evaluation of the spatially resolved fluorescence in confocal sections of intact spheroids during irradiation. The PDT efficacy comparisons establish that mTHPC's enhanced potency may be accounted for completely on the basis of its ability to sequester tightly in cells and its photophysical properties, in particular its higher extinction coefficient at a redshifted wavelength. We extend the efficacy comparison to include the influence of hemoglobin absorption of PDT treatment light and show that incorporating the influence of wavelength-dependent light attenuation in tissue further contributes to significantly higher efficacy for mTHPC- vs Photofrin-PDT.
中-四羟基苯基二氢卟吩（mTHPC）是目前可用于临床光动力疗法（PDT）的最有效的光敏剂之一。然而，其高光动力疗效的原因仍未得到解决。为了研究mTHPC与血卟啉衍生物（Photofrin）的光动力疗法疗效，我们利用从球体氧电极测量分析中提取的光物理参数知识，来计算和比较它们各自的单线态氧（1O2）剂量沉积。电极测量间接报告了mTHPC的漂白动力学，并表明其光漂白机制与1O2介导的反应一致。通过对完整球体照射期间共聚焦切片中空间分辨荧光的更直接评估，证实了mTHPC通过1O2反应的光降解。光动力疗法疗效比较表明，mTHPC增强的效力可能完全基于其在细胞中紧密螯合的能力及其光物理性质，特别是其在红移波长处更高的消光系数。我们将疗效比较扩展到包括血红蛋白对光动力疗法治疗光吸收的影响，并表明纳入组织中波长依赖性光衰减的影响进一步显著提高了mTHPC与血卟啉衍生物光动力疗法的疗效。
