Image-Based Quantification of Benzoporphyrin Derivative Uptake, Localization, and Photobleaching in 3D Tumor Models, for Optimization of PDT Parameters.
Image-Based Quantification of Benzoporphyrin Derivative Uptake, Localization, and Photobleaching in 3D Tumor Models, for Optimization of PDT Parameters.
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作者：
Glidden MD;Celli JP;Massodi I;Rizvi I;Pogue BW;Hasan T
光动力疗法（PDT）是一种基于光的治疗方式，其中光敏剂（PS）的波长特异性激活在照射区域产生细胞毒性反应。PDT反应主要取决于几个参数，包括光剂量、PS剂量、摄取时间、注量率和光递送模式。虽然这些治疗参数的系统优化可能是复杂的，但它也提供了多种途径来增强不同治疗条件下的PDT疗效，前提是建立合理的框架来量化参数选择对治疗反应的影响。在这里，我们提出了一种治疗诊断技术，结合了PS的固有能力，同时作为一种治疗和成像剂，在三维（3D）体外肿瘤模型中使用基于图像的治疗评估，包括一个平台，以评估PDT参数对治疗结果的影响。我们使用这种方法来可视化和量化的PS苯并卟啉衍生物单酸环-A（BPD）的吸收，定位和光漂白的治疗条件范围内的不同的吸收时间，以及连续和分级的光输送方案在三维培养的AsPC-1和PANC-1细胞。根据光漂白模式和与细胞毒性反应的相关性，发现在4小时BPD摄取时的不对称分级光递送是评估的最有效方案。多细胞结节内细胞杀伤的空间分布的定量显示，这些条件也实现了沿3D结节的径向轴沿着的细胞毒性的最高深度。这里介绍的框架提供了一种方法，系统评估PDT治疗参数的生物相关的三维肿瘤模型，具有更广泛的应用到其他系统的潜力。
Photodynamic therapy (PDT) is a light-based treatment modality in which wavelength specific activation of a photosensitizer (PS) generates cytotoxic response in the irradiated region. PDT response is critically dependent on several parameters including light dose, PS dose, uptake time, fluence rate, and the mode of light delivery. While the systematic optimization of these treatment parameters can be complex, it also provides multiple avenues for enhancement of PDT efficacy under diverse treatment conditions, provided that a rational framework is established to quantify the impact of parameter selection upon treatment response. Here we present a theranostic technique, combining the inherent ability of the PS to serve simultaneously as a therapeutic and imaging agent, with the use of image-based treatment assessment in three dimensional (3D) in vitro tumor models, to comprise a platform to evaluate the impact of PDT parameters on treatment outcomes. We use this approach to visualize and quantify the uptake, localization, and photobleaching of the PS benzoporphyrin derivative monoacid ring-A (BPD) in a range of treatment conditions with varying uptake times as well as continuous and fractionated light delivery regimens in 3D cultures of AsPC-1 and PANC-1 cells. Informed by photobleaching patterns and correlation with cytotoxic response, asymmetric fractionated light delivery at 4 hours BPD uptake was found to be the most effective regimen assessed. Quantification of the spatial profile of cell killing within multicellular nodules revealed that these conditions also achieve the highest depth of cytotoxicity along the radial axis of 3D nodules. The framework introduced here provides a means for systematic assessment of PDT treatment parameters in biologically relevant 3D tumor models with potential for broader application to other systems.
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影响因子：
3.3
作者：
MILLER, GG;BROWN, K;MCPHEE, MS
通讯作者：
MCPHEE, MS
影响因子：
2.1
作者：
van den Boogert, J;van Staveren, HJ;van Hillegersberg, R
通讯作者：
van Hillegersberg, R
影响因子：
3.4
作者：
Pogue, BW;Hasan, T
通讯作者：
Hasan, T
影响因子：
3.5
作者：
NICHOLS, MG;FOSTER, TH
通讯作者：
FOSTER, TH
DOI：
10.1016/s1011-1344(00)00120-2
发表时间：
2000-11-01
影响因子：
5.4
作者：
Curnow, A;Haller, JC;Bown, SG
通讯作者：
Bown, SG