A Singlet Molecular Oxygen Imaging Sensor for Photodynamic Therapy

项目概述/摘要：光动力疗法（PDT）是一种很有前途的癌症治疗方法。PDT利用光敏剂如血卟啉衍生物（HPD）和其他化合物的亲和力，选择性地保留在恶性肿瘤中。当用光敏剂预处理的肿瘤用可见光照射时，发生光化学反应，肿瘤细胞被破坏。处于亚稳单线态δ态O2（1?）的氧分子被认为是在PDT过程中破坏癌细胞的物种。在第一阶段的提案中，物理科学公司（PSI）建议开发一种基于光学的监测器，该监测器将对光敏剂和单线态氧发射的空间范围和位置进行成像。该系统将建立在我们最近的结果之上，这些结果已经证明了观察PDT过程中产生的单线态氧光发射的能力。该系统将使用光纤耦合脉冲二极管激光器和最先进的商业化2-D成像相机来开发和演示PDT过程中光敏剂浓度和单线态氧气产生的空间成像。该系统将在PSI的体外样本上进行开发和测试，然后与我们的第一阶段合作伙伴一起运往达特茅斯学院进行体内测试。这些测试的目的是证明第一阶段成像设备可以绘制肿瘤内单线态氧气产生的空间位置，并将其与光敏剂的空间分布相关联。在第二阶段，我们将在达特茅斯学院和马萨诸塞州总医院进行广泛的测试，设计、制造和测试一种便携式、坚固耐用的仪器。一个完全开发的仪器将是PDT研究的几个方面的有价值的工具，包括：阐明动力学和生理现象，评估针对特定组织区域的新型光敏剂，将光敏剂浓度与单线态氧产生相关联，以及识别肿瘤坏死机制。项目描述：与公共卫生的相关性：该项目将展示一种新的诊断方法，通过光激活抗癌药物改善癌症的治疗。一个成功的程序将产生高分辨率的激发形式的氧气（由肿瘤内的光激活药物产生）的位置图像，这些氧气负责杀死肿瘤。它将成为开发新的、更有效的治疗方法的宝贵研究工具。

DESCRIPTION (provided by applicant): Project Summary/Abstract: Photodynamic therapy (PDT) is a promising cancer treatment. PDT uses the affinity of photosensitizers such as hematoporphyrin derivative (HPD) and other compounds to be selectively retained in malignant tumors. When tumors, pretreated with the photosensitizer, are irradiated with visible light, a photochemical reaction occurs and tumor cells are destroyed. Oxygen molecules in the metastable singlet delta state O2(1?) are believed to be the species that destroys cancerous cells during PDT. In this Phase I proposal, Physical Sciences Inc. (PSI) proposes to develop an optically-based monitor that will image the spatial extent and location of both the photosensitizer and singlet oxygen emission. The system will build upon our recent results that have demonstrated the ability to observe singlet oxygen optical emission in-vivo produced during PDT. The system will use a fiber coupled, pulsed diode laser and a state-of-the-art, just commercially introduced 2-D imaging camera to develop and demonstrate spatial imaging of photosensitizer concentration and singlet oxygen production during PDT. The system will be developed and tested on in-vitro samples at PSI then transported to Dartmouth College for in-vivo testing in collaboration with our Phase I partners. The goal of these tests is to demonstrate that the Phase I imaging device can map the spatial location of the singlet oxygen production within the tumors and correlate it with the spatial distribution of the photosensitizer. In Phase II, we will design, build, and test a portable, ruggedized instrument through extensive tests both at Dartmouth College and the Massachusetts General Hospital. A fully developed instrument will be a valuable tool for several aspects of PDT research including: elucidating kinetic and physiological phenomena, assessing new photosensitizers targeted to specific tissue areas, correlating photosensitizer concentrations with singlet oxygen production, and discerning mechanisms of tumor necrosis. Project Narrative: Relevance to public health: This project will demonstrate a novel diagnostic for improving the treatment of cancer by light activated cancer killing drugs. A successful program will produce high resolution images of the location of an excited form of oxygen (produced by the light activated drugs within tumors) that is responsible for killing the tumor. It will be a valuable research tool to develop new, more effective treatments.