Henderson Barbara W, Busch Theresa M, Snyder John W
Department of Cell Stress Biology, The Photodynamic Therapy Center, Roswell Park Cancer Institute, Buffalo, New York, New York 14263, USA.
Lasers Surg Med. 2006 Jun;38(5):489-93. doi: 10.1002/lsm.20327.
Molecular oxygen in the tissue to be treated by photodynamic therapy (PDT) is critical for photodynamic cell killing. The fluence rate of PDT light delivery has been identified as an important modulator of tissue oxygenation and treatment outcome. This article provides supporting evidence for the role of fluence rate in PDT and discusses the underlying mechanisms.
STUDY DESIGN/MATERIALS AND METHODS: Intratumoral pO2 was measured polarographically in murine tumors before and during PDT light treatment using the Eppendorf pO2 Histograph. Tumor response as a function of fluence rate and fluence was also assessed in murine tumor models. Changes in vascular permeability as a function of fluence rate were determined in murine tumors by measuring tumor uptake of fluorescent beads (200 nm diameter).
Severe oxygen depletion is shown to occur within seconds of illumination at a fluence rate of 75 mW/cm2 in radiation-induced fibrosarcoma (RIF) tumors photosensitized with AlPcS2. This effect was reversible and consistent with photochemical oxygen depletion, which has been shown by us and others to be fluence rate dependent. It is demonstrated that fluence rate affects the PDT tumor response in the Colon 26 tumor model, high fluence rate diminishing or even totally inhibiting tumor control, low fluence rate promoting tumor control. The influence of fluence rate is not restricted to cytocidal effects, but can also be seen in sublethal conditions such as vascular permeability.
Fluence rate of PDT light delivery exerts far-reaching control upon treatment outcome through its oxygenation modulating properties and possibly other mechanisms yet to be identified. This has been shown to be true in the preclinical and clinical setting. Further development of in situ dosimetry will be necessary to take full advantage of these discoveries.
光动力疗法（PDT）治疗的组织中的分子氧对于光动力细胞杀伤至关重要。已确定PDT光递送的光通量率是组织氧合和治疗结果的重要调节因素。本文为光通量率在PDT中的作用提供了支持证据，并讨论了潜在机制。
研究设计/材料与方法：使用Eppendorf pO2组织氧测定仪在PDT光治疗前和治疗期间以极谱法测量小鼠肿瘤内的pO2。还在小鼠肿瘤模型中评估了作为光通量率和光通量函数的肿瘤反应。通过测量荧光珠（直径200 nm）的肿瘤摄取来确定小鼠肿瘤中作为光通量率函数的血管通透性变化。
在用AlPcS2光敏化的辐射诱导纤维肉瘤（RIF）肿瘤中，以75 mW/cm2的光通量率照射后数秒内就会出现严重的氧耗竭。这种效应是可逆的，并且与光化学氧耗竭一致，我们和其他人已证明光化学氧耗竭依赖于光通量率。结果表明，光通量率会影响结肠26肿瘤模型中的PDT肿瘤反应，高光通量率会减弱甚至完全抑制肿瘤控制，低光通量率则促进肿瘤控制。光通量率的影响不仅限于细胞杀伤作用，在诸如血管通透性等亚致死条件下也可以看到。
PDT光递送的光通量率通过其氧合调节特性以及可能尚未确定的其他机制对治疗结果产生深远影响。这在临床前和临床环境中已得到证实。有必要进一步开发原位剂量测定法以充分利用这些发现。
