Impact of treatment response metrics on photodynamic therapy planning and outcomes in a three-dimensional model of ovarian cancer
Impact of treatment response metrics on photodynamic therapy planning and outcomes in a three-dimensional model of ovarian cancer
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DOI：
10.1117/1.jbo.18.9.098004
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发表时间：
2013-09-01
影响因子：
3.5
通讯作者：
Hasan, Tayyaba
中科院分区：
文献类型：
--
作者：
Anbil, Sriram;Rizvi, Imran;Hasan, Tayyaba
基于形态学成像表征治疗效果的常用方法可能会歪曲结果并排除有效的治疗方法。使用卵巢癌三维模型，两个功能性治疗反应指标用于评估光动力疗法（PDT）疗效：由活细胞和非活细胞计算的总体积，以及由活细胞计算的活体积。利用独立的光动力学活性报告证实了这些基于体积的指标的效用：活力，常见的基于荧光的比率分析和光敏剂光漂白，其特征是部分由于PDT期间活性物质的产生而导致荧光损失。活体积与光漂白和活力相关，这表明它比总体积更能反映PDT的疗效，而总体积与任何一个指标都不相关。基于这些发现，利用活体积和活力来探测肿瘤群体对0.25、1和10 μ M苯并卟啉衍生物（BPD）给药的PDT剂量参数的敏感性。0.25 μ M / BPD的PDT最显著地降低了活体积和生存能力，并导致了小结节的显著转变。越来越复杂的生物工程模型可以补充当前的治疗计划方法，并提供独特的机会来批判性地评估关键参数，包括治疗反应的指标。(C) 2013年中国光学仪器工程师学会
Common methods to characterize treatment efficacy based on morphological imaging may misrepresent outcomes and exclude effective therapies. Using a three-dimensional model of ovarian cancer, two functional treatment response metrics are used to evaluate photodynamic therapy (PDT) efficacy: total volume, calculated from viable and nonviable cells, and live volume, calculated from viable cells. The utility of these volume-based metrics is corroborated using independent reporters of photodynamic activity: viability, a common fluorescence-based ratiometric analysis, and photosensitizer photobleaching, which is characterized by a loss of fluorescence due in part to the production of reactive species during PDT. Live volume correlated with both photobleaching and viability, suggesting that it was a better reporter of PDT efficacy than total volume, which did not correlate with either metric. Based on these findings, live volume and viability are used to probe the susceptibilities of tumor populations to a range of PDT dose parameters administered using 0.25, 1, and 10 mu M benzoporphyrin derivative (BPD). PDT with 0.25 mu M BPD produces the most significant reduction in live volume and viability and mediates a substantial shift toward small nodules. Increasingly sophisticated bioengineered models may complement current treatment planning approaches and provide unique opportunities to critically evaluate key parameters including metrics of therapeutic response. (C) 2013 Society of Photo-Optical Instrumentation Engineers (SPIE)