Insights into Photodynamic Therapy Dosimetry: Simultaneous Singlet Oxygen Luminescence and Photosensitizer Photobleaching Measurements
Insights into Photodynamic Therapy Dosimetry: Simultaneous Singlet Oxygen Luminescence and Photosensitizer Photobleaching Measurements
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DOI：
10.1016/j.bpj.2011.12.043
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发表时间：
2012-02-08
影响因子：
3.4
通讯作者：
Wilson, Brian C.
中科院分区：
文献类型：
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作者：
Jarvi, Mark T.;Patterson, Michael S.;Wilson, Brian C.
光动力疗法（PDT）通常基于通过光敏剂、光和氧（O-3（2））的相互作用产生高活性单线态氧（O-1（2））。这三个组成部分是高度相互依赖和动态的，导致可变的时间和空间的O-1（2）剂量沉积。考虑到这种复杂性的强大剂量测定可以改善治疗结果。尽管O-1（2）的1270 nm发光发射提供了直接和预测的PDT剂量度量，但它可能不具有临床实用性。我们使用O-1（2）发光（或单线态氧发光（SOL））作为金标准度量，以评估基于光敏剂漂白的潜在临床可行剂量测定法。我们使用光敏剂间-四（羟基苯基）二氢卟酚（mTHPC），在各种条件下（包括变量O-3（2））同时测量SOL和光敏剂荧光，进行了体外剂量反应研究。结果表明，SOL总是预测细胞毒性和免疫PDT的复杂动力学，而光漂白为基础的剂量测定在缺氧条件下失败。然而，我们确定了mTHPC的先前未报告的613 nm发射，表明O-3（2）水平极低，可用于补救基于光漂白的剂量测定。这些研究提高了我们对PDT过程的理解，证明SOL是一个有价值的金标准剂量度量，并表明当明智地使用时，光漂白可以作为O-1（2）剂量的替代品。
Photodynamic therapy (PDT) is generally based on the generation of highly reactive singlet oxygen (O-1(2)) through interactions of photosensitizer, light, and oxygen (O-3(2)). These three components are highly interdependent and dynamic, resulting in variable temporal and spatial O-1(2) dose deposition. Robust dosimetry that accounts for this complexity could improve treatment outcomes. Although the 1270 nm luminescence emission from O-1(2) provides a direct and predictive PDT dose metric, it may not be clinically practical. We used O-1(2) luminescence (or singlet oxygen luminescence (SOL)) as a gold-standard metric to evaluate potentially more clinically feasible dosimetry based on photosensitizer bleaching. We performed in vitro dose-response studies with simultaneous SOL and photosensitizer fluorescence measurements under various conditions, including variable O-3(2), using the photosensitizer meta-tetra(hydroxyphenyl)chlorin (mTHPC). The results show that SOL was always predictive of cytotoxicity and immune to PDT's complex dynamics, whereas photobleaching-based dosimetry failed under hypoxic conditions. However, we identified a previously unreported 613 nm emission from mTHPC that indicates critically low O-3(2) levels and can be used to salvage photobleaching-based dosimetry. These studies improve our understanding of PDT processes, demonstrate that SOL is a valuable gold-standard dose metric, and show that when used judiciously, photobleaching can serve as a surrogate for O-1(2) dose.