Explicit dosimetry for photodynamic therapy: macroscopic singlet oxygen modeling.

Explicit dosimetry for photodynamic therapy: macroscopic singlet oxygen modeling.
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DOI:
10.1002/jbio.200900101
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发表时间:
2010-06
影响因子:
2.8
通讯作者:
Zhu, Timothy C.
Zhu, Timothy C.
中科院分区:
物理与天体物理2区
文献类型:
--
作者:
Wang, Ken Kang-Hsin;Finlay, Jarod C.;Busch, Theresa M.;Hahn, Stephen M.;Zhu, Timothy C.

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单线态氧(1O2)是ii型光动力治疗(PDT)中杀死细胞的主要细胞毒性物质。提出了一个经验的四参数宏观模型来计算“表观反应1O2浓度”[1O2]rx作为临床PDT剂量学量。该模型结合了光扩散方程和一组PDT动力学方程,可应用于任何临床治疗几何。我们证明,通过引入拟合量“表观单线态氧阈浓度”[1O2]rx,sd,可以通过将计算得到的[1O2]rx拟合到每只小鼠中使用间质测量的Photofrin浓度和光学性质的Photofrin介导的pdt诱导坏死距离来确定模型参数。在确定模型参数和[1O2]rx,sd后,我们期望使用该模型作为明确的剂量学来评估特定光敏剂在体内环境中的PDT治疗结果。结果还提供证据表明,由于考虑了耗氧量(或光通量)效应,[1O2]rx可以比PDT剂量更好地预测PDT结果,PDT剂量定义为光敏剂吸收的能量,与光敏剂浓度和光通量的乘积成正比。
Singlet oxygen (1O2) is the major cytotoxic agent responsible for cell killing for type-II photodynamic therapy (PDT). An empirical four-parameter macroscopic model is proposed to calculate the “apparent reacted 1O2 concentration”, [1O2]rx, as a clinical PDT dosimetry quantity. This model incorporates light diffusion equation and a set of PDT kinetics equations, which can be applied in any clinical treatment geometry. We demonstrate that by introducing a fitting quantity “apparent singlet oxygen threshold concentration” [1O2]rx,sd, it is feasible to determine the model parameters by fitting the computed [1O2]rx to the Photofrin-mediated PDT-induced necrotic distance using interstitially-measured Photofrin concentration and optical properties within each mouse. After determining the model parameters and the [1O2]rx,sd, we expect to use this model as an explicit dosimetry to assess PDT treatment outcome for a specific photosensitizer in an in vivo environment. The results also provide evidence that the [1O2]rx, because it takes into account the oxygen consumption (or light fluence rate) effect, can be a better predictor of PDT outcome than the PDT dose defined as the energy absorbed by the photosensitizer, which is proportional to the product of photosensitizer concentration and light fluence.
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