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

描述(申请人提供)：光动力疗法(PDT)是一种很有前途的癌症治疗方法。PDT利用光敏剂的亲和力，如血卟啉衍生物(HPD)和其他化合物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，肿瘤细胞被摧毁。处于亚稳态的单重态O2(1)的氧分子被认为是在光动力疗法中摧毁癌细胞的物种。一种基于光学的成像设备可以可视化光动力疗法中单线态氧的产生和PS在肿瘤中的位置的空间地图，将是光动力疗法研究和更有效的治疗的有价值的工具。在第一阶段计划中，物理科学公司(PSI)开发和演示了一种2D成像系统，并成功地在体外和体内产生了光敏剂和单线态氧的空间分辨率图像。体内图像来自于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建议设计、制造和测试一种完整的、坚固耐用的2D成像传感器，用于同时、共同注册的单线态氧发射和PS荧光。该系统将使用光纤耦合半导体激光器进行光照射，并使用两个采用光谱辨别方法的CCD摄像机。一种新型的增强型近红外阵列相机将用于单线态氧发射的探测。单线态氧发射的二维空间分辨图像将与可见光成像相机获得的PS荧光相关联。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一起在实验室大鼠的肿瘤模型上进行全面的体内测试。一种完全开发的仪器将是光动力疗法研究的几个方面的宝贵工具，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，光敏剂浓度与单线态氧产生的关联，以及评估单线态氧产生与肿瘤消退的关系。公共卫生相关性：该项目将展示一种新的诊断方法，用于改善光激活抗癌药物治疗癌症的效果。一个成功的程序将产生高分辨率的氧气激发形式(由肿瘤内的光激活药物产生)位置的高分辨率图像，该氧负责杀死肿瘤。这将是开发新的、更有效的治疗方法的有价值的研究工具。

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.