Lilge L, Molpus K, Hasan T, Wilson B C
Ontario Cancer Institute/Princess Margaret Hospital, Department of Medical Biophysics, University of Toronto, Canada.
Photochem Photobiol. 1998 Sep;68(3):281-8.
Few studies have been published to date measuring spatially resolved fluence rates in complex tissue geometries. Here the light distributions of three different intraperitoneal light delivery geometries in a murine ovarian cancer model were investigated to assess their influence on the tumorcidal efficacy of photodynamic therapy (PDT). In vivo fluence rate measurements in the peritoneal cavities of mice, with the light intensity being mapped in three transverse planes, were performed using fiber-optic detectors. Three different source fiber designs and placements were tested for their ability to provide uniform irradiation of the peritoneal cavity. The biological response to a PDT protocol comprising three separate treatments administered at 72 h intervals, each consisting of a 0.25 mg kg-1 intraperitoneal injection of benzoporphyrin derivative-mono acid ring A followed 90 min later by delivery of 15 J of 690 nm light, was measured. The tissue response was evaluated by measuring the number of remaining visible lesions and the total residual tumor mass. Fluence rate measurements showed large variations in the fluence rate distribution for similar intended treatments. The most uniform and reproducible illumination was achieved using two 18 mm long cylindrical emitting optical fibers. The biological response was comparable to that produced when a flat-cleaved end optical fiber is used to illuminate the four quadrants of the abdomen sequentially. While a good reproducibility in tumor induction in this animal model exists, no correlation was found between the fluence rate distribution measured in one group of animals and the biological response in a separate group of similarly treated animals. Due to the large intra-animal variability in fluence rate distribution, representative fluence rate mapping in complex tissue geometries is of limited value when applied to an individual PDT treatment. Thus, surveillance of the fluence rate during individual treatments will be required for acceptable PDT dosimetry. To improve the versatility of this particular animal model for PDT research, a large number of extended sources are required to increase uniformity of the illumination in order to reduce unwanted cytotoxic side effects resulting from foci of high fluence rates. In this way, subsequent increase of the total energy delivered to the tumor may be possible.
迄今为止，很少有研究发表来测量复杂组织几何结构中的空间分辨通量率。在此，研究了小鼠卵巢癌模型中三种不同腹腔内光传输几何结构的光分布，以评估它们对光动力疗法（PDT）杀肿瘤效果的影响。使用光纤探测器在小鼠腹腔内进行体内通量率测量，在三个横向平面上绘制光强分布图。测试了三种不同的源光纤设计和放置方式，以评估它们提供腹腔均匀照射的能力。测量了对一种PDT方案的生物学反应，该方案包括每隔72小时进行三次单独治疗，每次治疗包括腹腔注射0.25mg/kg苯卟啉衍生物单酸环A，90分钟后给予15J的690nm光。通过测量剩余可见病变的数量和总残余肿瘤质量来评估组织反应。通量率测量表明，对于类似的预期治疗，通量率分布存在很大差异。使用两根18mm长的圆柱形发射光纤可实现最均匀和可重复的照明。生物学反应与使用平切端光纤依次照射腹部四个象限所产生的反应相当。虽然在该动物模型中肿瘤诱导具有良好的可重复性，但在一组动物中测量的通量率分布与另一组接受类似治疗的动物的生物学反应之间未发现相关性。由于动物体内通量率分布的巨大变异性，在应用于个体PDT治疗时，复杂组织几何结构中的代表性通量率映射价值有限。因此，为了获得可接受的PDT剂量测定，需要在个体治疗期间监测通量率。为了提高这种特定动物模型在PDT研究中的通用性，需要大量扩展光源来提高照明的均匀性，以减少由高通量率焦点引起的不必要的细胞毒性副作用。通过这种方式，随后增加传递到肿瘤的总能量可能是可行的。
