Optical Dosimeter-guided Photodynamic Therapy

光动力疗法(PDT)是一种很有前途的癌症治疗方法。空气中的氧分子 亚稳态单重态O2(1Δ)被认为是在 光动力疗法。尽管靶向PDT的好处是选择性地杀灭肿瘤，对周围环境的影响最小 健康的组织，目前很难，如果不是不可能的话，预测一个人对 光动力疗法。这抑制了PDT临床应用的接受度。在NCI SBIR资助下，实物 Science Inc.(PSI)已经开发了两种用于PDT的原型机，可在体内使用：一种非成像的超剂量计 基于光电倍增管(PMT)的单线态氧检测灵敏点传感器和二维成像传感器 用于PS荧光和单线态O2检测。这些设备使用光谱和时间分辨 方法优化敏感度。我们提议的计划的总体目标是产生一个完整的、 成像PDT系统将使用实时反馈来控制治疗过程中的PDT光剂量。 在第一阶段，我们将开发和测试一种新引入的2D成像相机，它包含以下门控 一微秒和快速的成帧速率。这将使单线态氧的灵敏度提高至少一个数量级 规模之大。该系统将基于PSI目前的2D成像系统系统平台 已经证明了在体内观察PDT过程中产生的单线态O2和PS荧光的能力。这个 目前的系统使用近红外(NIR)敏感相机拍摄单线态O2图像。然而，这台摄像机 没有快速时间门控能力，这限制了检测方法仅限于光谱 歧视。该系统将在PSI的体外样本上进行开发和测试，然后被运送到 达特茅斯学院的活体测试。第一阶段的研究结果将用于设计第二阶段的系统 用于PDT治疗和剂量计。光纤耦合脉冲半导体激光器将用于PDT 激励源。第一阶段研究的目标是证明新的检测灵敏度 介绍了集成在PSI检测系统中的2D摄像头。在第二阶段，联合PDT系统将 为体外和体内研究进行广泛的性能验证而设计、建造和测试。一个 精确的剂量计优化PDT的个体化治疗反应是提高疗效的必要手段。 光动力疗法在临床环境中的结果。一个完全开发的仪器首先将是PDT的有价值的工具 研究人员和随后用于临床的PDT使用。

Photodynamic Therapy (PDT) is a promising modality for cancer treatment. Oxygen molecules in the metastable singlet delta state O2(1Δ) are believed to be the species that destroys cancerous cells during PDT. Despite the benefit of targeted PDT that kills tumors selectively with minimum effect on surrounding healthy tissues, at the present time it is difficult, if not impossible, to predict the response of an individual to PDT. This has inhibited the acceptance of PDT for clinical uses. Under NCI SBIR funding, Physical Sciences Inc. (PSI) has developed two prototype, in vivo capable dosimeters for PDT: a non-imaging ultra- sensitive photomultiplier tube (PMT)-based point sensor for singlet O2 detection and a 2D imaging sensor for PS fluorescence and singlet O2 detections. These devices use spectral and temporal discrimination methods to optimize sensitivity. The overall goal of our proposed program is to produce an integrated, imaging PDT system that will use real-time feedback to control PDT light dose during the treatment. In Phase I, we will develop and test a newly introduced 2D imaging camera that incorporates gating below a microsecond and a fast framing rate. This will enhance the sensitivity singlet oxygen by at least an order of magnitude. The system will be based upon PSI's current system platform of the 2D imaging system that has demonstrated the ability to observe singlet O2 and PS fluorescence in vivo produced during PDT. The current system uses a near infrared (NIR) sensitive camera for singlet O2 images. However, this camera does not have a fast time-gating capability, and that limits the detection method to only spectral discrimination. The system will be developed and tested on in vitro samples at PSI then transported to Dartmouth College for in vivo testing. The Phase I study result will be utilized to design a Phase II system for both PDT treatments and dosimeters. A fiber-coupled pulsed diode laser will be used for the PDT excitation source. The goal of the Phase I study is to demonstrate the detection sensitivity of the newly introduced 2D camera integrated in the PSI detection system. In Phase II the combined PDT system will be designed, built, and tested for extensive performance verification for in vitro and in vivo studies. An accurate dosimeter to optimize the individual treatment response of PDT is necessary to improve the outcomes of PDT in a clinical environment. A fully developed instrument will be a valuable tool first for PDT researchers and subsequently for clinical PDT uses.