Singlet Molecular Imaging Sensor for Photodynamic Therapy (7218-060)

描述（由申请人提供）：光动力疗法（PDT）是一种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（PS）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。处于亚稳态单线态δ状态O2（1）的氧分子被认为是在PDT期间破坏癌细胞的物质。基于光学的成像装置可以可视化PDT期间肿瘤中单线态氧产生和PS位置的空间图，这将是PDT研究和更有效治疗的有价值工具。在第一阶段计划物理科学公司。(PSI)开发并展示了一个二维成像系统，并成功地产生了空间分辨图像的光敏剂和单线态氧在体外和体内。体内图像来自含有肿瘤模型的小鼠。基于这些成功的第一阶段结果，在第二阶段，PSI提出设计，建造和测试一个完整的和坚固的2D成像传感器，用于同时，共同登记的单线态氧发射和PS荧光。该系统将使用一个光纤耦合二极管激光器的光照射和两个CCD相机的光谱鉴别方法。一种新的，加强，近红外阵列相机将用于检测单线态氧的排放。单线态氧发射的2D空间分辨图像将与用可见光成像相机获得的PS荧光相关。该系统将在PSI的体外光敏剂样品上进行测试。我们还将与达特茅斯学院的合作者在实验室大鼠的肿瘤模型上进行全面的体内测试。一个完全开发的仪器将是一个有价值的工具，PDT研究的几个方面，包括：阐明动力学和生理现象，评估新的光敏剂针对特定的组织区域，相关的光敏剂浓度与单线态氧生产，并评估单线态氧生产与肿瘤消退之间的关系。公共卫生相关性：该项目将展示一种新的诊断方法，用于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图像的位置的激发形式的氧气（产生的光激活药物在肿瘤内），负责杀死肿瘤。这将是一个有价值的研究工具，以开发新的，更有效的治疗。

DESCRIPTION (provided by applicant): 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 (PS), 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. An optically- based imaging device that can visualize spatial maps of both the singlet oxygen production and the location of the PS in a tumor during PDT would be a valuable tool for PDT research and more effective treatments. In a Phase I program Physical Sciences Inc. (PSI) developed and demonstrated a 2D imaging system and successfully produced spatially resolved images of photosensitizers and singlet oxygen both in-vitro and in-vivo. The in-vivo images were from mice containing tumor models. Based on these successful Phase I results, in Phase II, PSI proposes to design, build and test a complete and ruggedized 2D imaging sensor for simultaneous, co-registered singlet oxygen emission and PS fluorescence. The system will use a fiber coupled diode laser for light irradiation and two CCD cameras with a spectral discrimination method. A novel, intensified, near-IR array camera will be used for the detection of singlet oxygen emission. The 2D spatially resolved image of singlet oxygen emission will be correlated with PS fluorescence obtained with a visible imaging camera. The system will be tested on in-vitro photosensitizer samples at PSI. Comprehensive in-vivo tests will also be performed on tumor models in laboratory rats with our collaborators at Dartmouth College. 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 evaluating the relationship between singlet oxygen production with tumor regression. PUBLIC HEALTH RELEVANCE: 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.