Preclinical Study of the Novel Vascular Occluding Agent, WST11, for Photodynamic Therapy of the Canine Prostate
Preclinical Study of the Novel Vascular Occluding Agent, WST11, for Photodynamic Therapy of the Canine Prostate
复制标题
DOI：
10.1016/j.juro.2011.03.039
复制
发表时间：
2011-07-01
影响因子：
6.6
通讯作者：
Elhilali, Mostafa
中科院分区：
文献类型：
--
作者：
Chevalier, Simone;Anidjar, Maurice;Elhilali, Mostafa
目的：WST09 的血管靶向光动力疗法显示出治疗放射后复发性前列腺癌的希望，但水溶液的疏水性限制了应用。我们测试了WST11（一种新型水溶性血管闭塞剂）用于狗前列腺血管靶向光动力治疗的安全性和有效性，并将其与WST09血管靶向光动力治疗进行比较。材料和方法：将光纤插入前列腺并连接到二极管激光器。在 10 分钟内，以不同剂量（包括无光照的药物对照）向 34 只狗输注 WST11（Steba Biotech，Cedex，法国），并在 3 只狗中输注 WST09（Steba Biotech）（2 mg/kg）。根据激光能量密度和传递的能量，照明在 5 或 10 分钟时启动，持续时间长达 33.2 分钟。收集血液用于分析和药代动力学。终点为1周。结果：未观察到与血管靶向光动力治疗相关的血压或血液检测值的变化。循环中的 WST11 随着药物输注而增加，并在 1 小时内迅速下降，到 24 小时达到不可检测的水平。除一只患有肠套叠的狗外，所有狗在血管靶向光动力治疗后均表现良好，只有轻微的泌尿系统症状，并在 24 至 48 小时内消失。肺和肝正常。除对照组外，所有前列腺均存在出血。这转化为 WST11 阈值和固定照明剂量窗口内的坏死。坏死与血管内皮层的损失相关。 Fluence高度影响坏死。 WST11 血管靶向光动力治疗与 WST09 血管靶向光动力治疗具有可比性，并且最佳消融每个叶约 5.0 cm(3) 的组织和整个前列腺约 10 cm(3)。结论：WST11 血管靶向光动力治疗在狗前列腺中的安全性和有效性支持前列腺癌和良性前列腺增生的临床应用。
Purpose: Vascular targeted photodynamic therapy with WST09 shows promise for recurrent prostate cancer after radiation but hydrophobicity in aqueous solutions limited application. We tested the safety and efficacy of WST11, a novel water soluble vascular occluding agent, for vascular targeted photodynamic therapy of the dog prostate and compared it to WST09 vascular targeted photodynamic therapy.Materials and Methods: Optical fibers were inserted in the prostate and connected to diode lasers. WST11 (Steba Biotech, Cedex, France) at varying doses, including a drug control with no light in 34 dogs, and WST09 (Steba Biotech) (2 mg/kg) in 3 dogs were infused during 10 minutes. Illumination was initiated at 5 or 10 minutes, and lasted up to 33.2 minutes based on laser fluence and delivered energy. Blood was collected for analysis and pharmacokinetics. The end point was at 1 week.Results: No vascular targeted photodynamic therapy associated change was observed in blood pressure or blood test values. Circulating WST11 increased with drug infusion and decreased rapidly during 1 hour to reach undetectable levels by 24 hours. All except 1 dog with bowel intussusception did well after vascular targeted photodynamic therapy with only mild urinary symptoms that resolved within 24 to 48 hours. Lung and liver were normal. Hemorrhage was present in all prostates except controls. This translated into necrosis at a WST11 threshold and within a window of doses at fixed illumination. Necrosis was associated with loss of the vessel endothelial layer. Fluence highly impacted necrosis. WST11 vascular targeted photodynamic therapy was advantageously comparable to WST09 vascular targeted photodynamic therapy, and optimally ablated about 5.0 cm(3) of tissue per lobe and about 10 cm(3) of the whole prostate.Conclusions: The safety and efficacy of WST11 vascular targeted photodynamic therapy in the dog prostate support clinical applications for prostate cancer and benign prostatic hyperplasia.