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首页> 外文会议>Optical methods for tumor treatment and detection: mechanisms and techniques in photodynamic therapy XXI >Tissue photosensitizer dosimetry using spectrally resolved fluorescence for pre-clinical and clinical verteporfin-PDT of pancreatic cancer
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Tissue photosensitizer dosimetry using spectrally resolved fluorescence for pre-clinical and clinical verteporfin-PDT of pancreatic cancer

机译：组织光敏剂量测定法使用光谱解析荧光进行胰腺癌临床前和临床Verteporfin-PDT

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Photodynamic therapy (PDT) mediated with verteporfin is currently being investigated to treat pancreatic cancer in patients who are not surgical candidates. Clinically, interstitial light delivery is administered through a fiber, via percutaneous needle implantation guided by ultrasound and/or verified by CT. Tumor response to PDT is based on photosensitizer (PS) dose, light dose, light dose rate and the timing of light application following PS injection. However, studies have shown that even when matching administered PDT treatment parameters such as drug dose and light level, there can be significant inter-patient variation in tissue damage post-PDT, and this has been primarily attributed to imprecise PS concentration at the target tissue site.In order to achieve optimal tumor response from PDT without causing major damage to surrounding tissue, it would be advantageous to measure the PS concentration in the target tissue just prior to light application. From these measurements, the clinician can adapt the light application dose to the measured target tissue PS concentration (i.e. insufficient target tissue PS concentrations compensated by higher light doses and vice versa) in order to provide an optimal light dose for each patient.In animal studies, a spectrometer-based in-vivo fluorescence dosimetry system has been used to assess accumulated PS levels (verteporfin) in situ. Measurements are taken from skin, leg muscle, buccal mucosa and tumor tissue locations one hour after injection of the photosensitizer. Real-time spectral fitting, subtraction of background autofluorescence and ratiometric analysis is performed on the raw data to extract out only the photosensitizer fluorescence and therefore concentration. Using a pre-measured calibration data set of varying concentrations for verteporfin in tissue phantoms composed of intralipid and whole blood, it was possible detect concentrations of the photosensitizer below 0.5nM.In the clinical studies being performed at UCL Hospital in which verteporfin-PDT treatment is being given to patients with pancreatic cancer, the dosimetry system is being used to assess PS concentration the pancreatic tumor tissue prior to interstitial light dose treatment. The goal of the work here is to determine whether the dosimetry system can accurately and efficiently be used clinically by evaluating the measured local tissue PS concentration to treatment outcome (area of necrosis established). The results of this study will partially determine the need for fluorescence dosimetry to individualize PDT treatment for patients based on local tissue PS concentration.
机译：Verteporfin介导的光动力疗法（PDT）目前正在研究，以治疗非手术候选人的胰腺癌。临床上，通过超声引导和/或CT验证的经皮针头植入，通过纤维进行组织间质光传输。肿瘤对PDT的反应基于光敏剂（PS）剂量，光剂量，光剂量率以及PS注射后的光照射时间。但是，研究表明，即使匹配给药的PDT治疗参数（如药物剂量和光照水平），PDT后患者的组织损伤也会有明显的变化，这主要归因于目标组织中PS浓度的不精确为了在不对周围组织造成重大损害的情况下实现来自PDT的最佳肿瘤反应，在光应用之前测量目标组织中PS的浓度将是有利的。通过这些测量，临床医生可以使光照射剂量适应所测得的目标组织PS浓度（即不足的目标组织PS浓度由较高的光剂量补偿，反之亦然），以便为每个患者提供最佳的光剂量。 ，基于光谱仪的体内荧光剂量测定系统已用于评估原位累积的PS水平（verteporfin）。注射光敏剂一小时后，从皮肤，腿部肌肉，颊粘膜和肿瘤组织位置进行测量。对原始数据进行实时光谱拟合，背景自发荧光扣除和比率分析，以仅提取光敏剂荧光并因此提取浓度。使用预先测定的校准数据集（由脂质内和全血组成的组织模型中的Verteporfin浓度变化），可以检测到光敏剂的浓度低于0.5nM。在UCL医院进行Verteporfin-PDT治疗的临床研究中对于胰腺癌患者，目前正在使用剂量测定系统评估间质光剂量治疗前胰腺肿瘤组织的PS浓度。此处的工作目标是通过评估针对治疗结果（已建立坏死区域）的局部组织PS浓度来确定剂量测定系统是否可以在临床上准确有效地使用。这项研究的结果将部分确定荧光剂量测定法的必要性，以根据局部组织PS浓度对患者进行PDT治疗。

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