Weersink Robert A, Bogaards Arjen, Gertner Mark, Davidson Sean R H, Zhang Kai, Netchev George, Trachtenberg John, Wilson Brian C
Laboratory for Applied Biophotonics, University Health Network, University Avenue, Toronto, Canada.
J Photochem Photobiol B. 2005 Jun 1;79(3):211-22. doi: 10.1016/j.jphotobiol.2005.01.008. Epub 2005 Mar 24.
Photodynamic therapy of solid organs requires sufficient PDT dose throughout the target tissue while minimizing the dose to proximal normal structures. This requires treatment planning for position and power of the multiple delivery channels, complemented by on-line monitoring during treatment of light delivery, drug concentration and oxygen levels. We describe our experience in implementing this approach in Phase I/II clinical trials of the Pd-bacteriophephorbide photosensitizer TOOKAD (WST09)-mediated PDT of recurrent prostate cancer following radiation failure. We present several techniques for delivery and monitoring of photodynamic therapy, including beam splitters for light delivery to multiple delivery fibers, multi-channel light dosimetry devices for monitoring the fluence rate in the prostate and surrounding organs, methods of measuring the tissue optical properties in situ, and optical spectroscopy for monitoring drug pharmacokinetics of TOOKAD in whole blood samples and in situ in the prostate. Since TOOKAD is a vascular-targeted agent, the design and implementation of the techniques are different than for cellular-targeted agents. Further development of these delivery and monitoring techniques will permit full on-line monitoring of the treatment that will enable real-time, patient-specific and optimized delivery of PDT.
实体器官的光动力疗法要求在整个靶组织中给予足够的光动力治疗剂量,同时将对近端正常结构的剂量降至最低。这需要针对多个输送通道的位置和功率进行治疗规划,并在治疗过程中对光输送、药物浓度和氧水平进行在线监测。我们描述了在I/II期临床试验中实施这种方法的经验,该试验采用钯细菌叶绿素光敏剂TOOKAD(WST09)介导的光动力疗法治疗放疗失败后的复发性前列腺癌。我们介绍了几种光动力治疗的输送和监测技术,包括用于将光输送到多根输送光纤的分束器、用于监测前列腺及周围器官中注量率的多通道光剂量测定装置、原位测量组织光学特性的方法,以及用于监测全血样本和前列腺原位中TOOKAD药物药代动力学的光谱学方法。由于TOOKAD是一种血管靶向剂,这些技术的设计和实施与细胞靶向剂不同。这些输送和监测技术的进一步发展将允许对治疗进行全面的在线监测,从而实现光动力治疗的实时、针对患者个体的优化输送。