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Comparison of actual and simulated tumoricidal effects induced by photodynamic therapy

机译：光动力疗法诱导的实际和模拟肿瘤效应的比较

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摘要

Objectives: Numerous studies employ mathematical methods, such as Monte Carlo simulation, to predict the tumor killing effects of photodynamic therapy (PDT) by simulating optical propagation, photosensitizer distribution, and oxygen distribution. Whether these models faithfully reflect tumor killing is unknown, and model validation using tumor cross sections in these studies is usually insufficient to answer this question. To fill this gap in our knowledge, we employed a mouse model of breast cancer to determine the spatiotemporal effects of PDT using direct histopathological and biochemical analyses of whole tumors.Methods: We prepared approximately 700 5-mu m-thick serial sections of breast tumors of syngeneic mice treated with PDT employing the photosensitizer photocarcinorin (PsD-007, a second-generation photosensitizer developed in China). Three adjoining sections were subjected to hematoxylin and eosin staining to assess necrosis, the TUNEL assay to evaluate apoptosis, and CD31 staining to detect angiogenesis, respectively. We then generated a three-dimensional (3D) reconstruction of the tumor to evaluate these processes. We simultaneously used the Monte Carlo method to develop a model of light distribution throughout the tumor to evaluate the actual and simulated tumor killing effects induced by PDT.Results: Tumor necrosis decreased exponentially as a function of distance from the source of illumination, while the distributions of apoptosis and neovascularization were independent of light distribution. Most apoptosis occurred in the lower layers (3000-4000 mu m) of the tumor where the light intensity was too low to excite the photosensitizer. Neovascularization occurred at depths ranging from 2500 to 3500 mu m. These analyses provided a 3D view of how a tumor is destroyed using PDT.Conclusions: Although the optical distribution model predicted tumor necrosis caused by PDT, it was ineffective in predicting the sites of apoptosis and vascular destruction. Mathematical modeling is limited in its capabilities required to gain a comprehensive understanding of the spatiotemporal events associated with PDT. The mouse model developed here will serve as a platform for detailed direct histopathological, biochemical, and molecular genetic analyses of the effects of PDT, which will facilitate the development of optimized treatment strategies.
机译：目的：许多研究采用数学方法，如蒙特卡罗模拟，通过模拟光学传播，光敏剂分布和氧气分布来预测光动力治疗（PDT）的肿瘤杀伤作用。这些模型是否忠实地反映肿瘤杀灭是未知的，并且在这些研究中使用肿瘤横截面的模型验证通常不足以回答这个问题。为了填补我们的知识，我们使用乳腺癌的小鼠模型，以确定PDT使用全肿瘤的直接组织病理学和生化分析来确定PDT的时空效应。方法：我们制备了大约700 5-mu m厚的乳腺肿瘤序列部分用PDT处理的Syngeecic小鼠用光敏化剂Photocarcinorin（PSD-007，在中国开发的第二代光敏剂）。将三个邻接部分进行苏木精和曙红染色，以评估坏死，调查分别评估细胞凋亡，以及CD31染色以检测血管生成。然后，我们产生了肿瘤的三维（3D）重建以评估这些过程。我们同时使用蒙特卡罗方法在整个肿瘤中发育光分布模型，以评估PDT诱导的实际和模拟肿瘤杀伤作用。结果：肿瘤坏死因距离照明源的距离而导致呈指数呈指数级，而分布细胞凋亡和新生血管形成与光分布无关。大多数细胞凋亡发生在肿瘤的下层（3000-4000 mu m）中，光强度太低而不能激发光敏剂。新生血管发生在深度范围为2500至3500亩。这些分析提供了一种3D视图，肿瘤如何使用PDT被破坏。结论：尽管光学分布模型预测PDT引起的肿瘤坏死，但预测细胞凋亡和血管破坏的部位是无效的。数学建模在其能力中受到限制，以全面了解与PDT相关的时空事件的全面了解。在此开发的小鼠模型将作为PDT的效果的详细直接组织病理学，生化和分子遗传学分析的平台，这将有助于开发优化的治疗策略。

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  • 来源
    《Photodiagnosis and Photodynamic Therapy》 |2020年第12期|102060.1-102060.9|共9页
  • 作者

    Jin Wendong; Shi Xiafei; Yin Huijuan; Zhang Haixia; Wang Zhiyuan; Chen Qianqian; Wu Hongjun; Han Yu; Li Yinxin;

  • 作者单位

    Chinese Acad Med Sci Peking Union Med Coll Inst Biomed Engn Laser Med Lab Tianjin 300192 Peoples R China;

    Chinese Acad Med Sci Peking Union Med Coll Inst Biomed Engn Laser Med Lab Tianjin 300192 Peoples R China;

    Chinese Acad Med Sci Peking Union Med Coll Inst Biomed Engn Laser Med Lab Tianjin 300192 Peoples R China;

    Tianjin Med Univ Biomed Engn & Technol Coll Tianjin 300070 Peoples R China;

    Nankai Univ Sch Phys Tianjin 370000 Peoples R China;

    Chinese Acad Med Sci Peking Union Med Coll Inst Biomed Engn Laser Med Lab Tianjin 300192 Peoples R China;

    Chinese Acad Med Sci Peking Union Med Coll Inst Biomed Engn Laser Med Lab Tianjin 300192 Peoples R China;

    Tianjin Med Univ Biomed Engn & Technol Coll Tianjin 300070 Peoples R China;

    Chinese Acad Med Sci Peking Union Med Coll Inst Biomed Engn Laser Med Lab Tianjin 300192 Peoples R China;

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  • 正文语种 eng
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  • 关键词

    Photodynamic therapy; Monte Carlo; Tumor damage; Necrosis; Apoptosis; Vascular destruction;

    机译：光动力疗法;蒙特卡洛;肿瘤损伤;坏死;凋亡;血管破坏;

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