Tetard Marie-Charlotte, Vermandel Maximilien, Leroy Henri-Arthur, Leroux Bertrand, Maurage Claude-Alain, Lejeune Jean-Paul, Mordon Serge, Reyns Nicolas
Univ. Lille, Inserm, CHU Lille, U1189 - ONCO-THAI - Image Assisted Laser Therapy for Oncology, F-59000 Lille, France; Department of Neurosurgery, CHU Lille, F-5900 Lille, France.
Univ. Lille, Inserm, CHU Lille, U1189 - ONCO-THAI - Image Assisted Laser Therapy for Oncology, F-59000 Lille, France; Department of Neurosurgery, CHU Lille, F-5900 Lille, France.
Photodiagnosis Photodyn Ther. 2016 Mar;13:218-224. doi: 10.1016/j.pdpdt.2015.07.169. Epub 2015 Jul 23.
Photodynamic therapy (PDT) has become a well-established modality for the treatment of many cancers. Photodynamic eradication of tumor cells depends on the presence of a photosensitizer, oxygen and light. However, oxygen depletion during PDT is a well known problem. Modulation of light delivery could address this issue by counteracting tumor hypoxia, thereby improving tumor cell killing. This preclinical study was designed to validate an animal model incorporating 5-aminolaevulinic acid (5-ALA)-PDT using U87 glioblastoma cells. We aimed to evaluate the effects of light modulation for inducing specific tumoral lesions in this model (i.e., necrosis or apoptosis).
U87 glioblastoma cells were stereotactically engrafted into the brains of male fox1 rnu/rnu rats. Light delivery was studied after 5-ALA injection (100 mg/kg i.p.). 26J of 635 nm light was interstitially delivered to U87 tumor-bearing rats at a radiant power of either 30 mW (high fluence rate) or 4.8 mW (low fluence rate). In each group, half of the population received illumination in 2 fractions with a refractory interval of 120 s, whereas the other half received continuous illumination.
Twenty-two animals received 5-ALA-PDT, and the level of necrosis was scored. In the high-fluence-rate group, we observed a greater degree of tumor necrosis in rats receiving fractionated delivery than in rats receiving continuous illumination. Similar differences were not observed in the low-fluence-rate group, which exhibited only sparse necrosis. Higher morbidity and mortality rates were observed in the high-fluence-rate group.
We have developed a reproducible and reliable rodent model for interstitial 5-ALA PDT. We found that the effects of 5-ALA-PDT are dependent on light delivery conditions. Although the low-fluence-rate treatment was better tolerated, 5-ALA-PDT induced more necrosis using fractionated delivery at a high fluence rate. These results require confirmation with further studies involving larger populations and additional fractionation schemes.
光动力疗法（PDT）已成为治疗多种癌症的成熟方法。光动力根除肿瘤细胞依赖于光敏剂、氧气和光的存在。然而，PDT 过程中的氧耗竭是一个众所周知的问题。调节光传递可以通过对抗肿瘤缺氧来解决这个问题，从而提高肿瘤细胞杀伤效果。本临床前研究旨在验证一种使用 U87 胶质母细胞瘤细胞的包含 5-氨基酮戊酸（5-ALA）-PDT 的动物模型。我们旨在评估光调节在该模型中诱导特定肿瘤病变（即坏死或凋亡）的效果。
将 U87 胶质母细胞瘤细胞立体定向植入雄性 fox1 rnu/rnu 大鼠的脑内。在注射 5-ALA（100mg/kg，腹腔注射）后研究光传递情况。以 30mW（高辐照率）或 4.8mW（低辐照率）的辐射功率将 26J 的 635nm 光间质内传递给携带 U87 肿瘤的大鼠。在每组中，一半的大鼠接受分两次照射，间隔 120s，而另一半接受连续照射。
22 只动物接受了 5-ALA-PDT，并对坏死程度进行了评分。在高辐照率组中，我们观察到接受分次照射的大鼠比接受连续照射的大鼠肿瘤坏死程度更高。在低辐照率组中未观察到类似差异，该组仅表现出稀疏的坏死。高辐照率组观察到更高的发病率和死亡率。
我们开发了一种用于间质内 5-ALA PDT 的可重复且可靠的啮齿动物模型。我们发现 5-ALA-PDT 的效果取决于光传递条件。尽管低辐照率治疗耐受性更好，但 5-ALA-PDT 在高辐照率下采用分次照射诱导了更多的坏死。这些结果需要通过涉及更大样本量和额外分次方案的进一步研究来证实。
