Fluence rate-dependent intratumor heterogeneity in physiologic and cytotoxic responses to Photofrin photodynamic therapy.
Fluence rate-dependent intratumor heterogeneity in physiologic and cytotoxic responses to Photofrin photodynamic therapy.
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DOI：
10.1039/b9pp00004f
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发表时间：
2009-12
期刊：
影响因子：
--
通讯作者：
Wang KK
中科院分区：
文献类型：
--
作者：
Busch TM;Xing X;Yu G;Yodh A;Wileyto EP;Wang HW;Durduran T;Zhu TC;Wang KK
光动力疗法（PDT）可导致在照射期间产生异质的、反应限制性缺氧，其可部分地通过照射注量率来控制。在本报告中，我们考虑1）缺氧，血管反应和细胞杀伤的区域差异作为肿瘤深度的函数和2）能量密度率作为深度依赖性区域内肿瘤异质性的介质的作用。皮内RIF鼠肿瘤用Photofrin-PDT处理，使用75或38 mW/cm 2辐照度的表面照射。通过比较肿瘤表面与基底（即沿着平行于皮肤表面且垂直于入射照明的平面）的影响来检查肿瘤反应的区域异质性。75 mW/cm 2-PDT在肿瘤基底相对于其表面产生显著更大的缺氧。增加缺氧的肿瘤基地不能归因于Photofrin浓度的区域差异，也不影响光化学耗氧量的注量率分布，但显着的深度依赖性异质性血管反应和细胞毒性反应检测。在较低的能量密度率为38 mW/cm 2时，缺氧或细胞毒性反应没有明显的可检测区域差异，血管反应的异质性显著低于75 mW/cm 2-PDT。这项研究表明，低通量率光动力疗法的益处部分是通过降低肿瘤内缺氧、血管和细胞毒性反应的异质性来介导的。
Photodynamic therapy (PDT) can lead to the creation of heterogeneous, response-limiting hypoxia during illumination, which may be controlled in part through illumination fluence rate. In the present report we consider 1) regional differences in hypoxia, vascular response, and cell kill as a function of tumor depth and 2) the role of fluence rate as a mediator of depth-dependent regional intratumor heterogeneity. Intradermal RIF murine tumors were treated with Photofrin-PDT using surface illumination at an irradiance of 75 or 38 mW/cm2. Regional heterogeneity in tumor response was examined through comparison of effects in the surface vs. base of tumors, i.e. along a plane parallel to the skin surface and perpendicular to the incident illumination. 75 mW/cm2-PDT created significantly greater hypoxia in tumor bases relative to their surfaces. Increased hypoxia in the tumor base could not be attributed to regional differences in Photofrin concentration nor effects of fluence rate distribution on photochemical oxygen consumption, but significant depth-dependent heterogeneity in vascular responses and cytotoxic response were detected. At a lower fluence rate of 38 mW/cm2, no detectable regional differences in hypoxia or cytotoxic responses were apparent, and heterogeneity in vascular response was significantly less than that during 75 mW/cm2-PDT. This research suggests that the benefits of low-fluence-rate-PDT are mediated in part by a reduction in intratumor heterogeneity in hypoxic, vascular and cytotoxic responses.
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影响因子：
8.8
作者：
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