Real Time, Automated Singlet Oxygen Dosimeter for PDT

用于 PDT 的实时、自动单线态氧剂量计

• 批准号: 7937338
• 负责人: STEVEN J DAVIS
• 金额: $ 11.66万
• 依托单位: PHYSICAL SCIENCES, INC
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7937338
• 关键词: Actinic keratosis; Age related macular degeneration; Animals; Area; Biological; Bladder; Borderline Personality Disorder; Brain; Bronchopulmonary Dysplasia; Calibration; Cancerous; Clinical; Clinical Research; Clinical Trials; Collaborations; Computer software; Coupled; Data; Databases; Detection; Development; Device Approval; Devices; Discrimination; Dose; Effectiveness; Elements; Esophageal; Evaluation; FDA approved; Fiber; Foundations; General Hospitals; Goals; Government; Grant; Hand; Human; Implant; In Vitro; Infusion procedures; Knowledge; Lasers; Learning; Letters; Licensing; Malignant Neoplasms; Malignant neoplasm of lung; Marketing; Massachusetts; Measurement; Methods; Modality; Modeling; Molecular; Monitor; Mus; Necrosis; Neoplasm Metastasis; Noise; Operative Surgical Procedures; Outcome; Outcome Measure; Oxygen; Performance; Persons; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phase II Clinical Trials; Photochemotherapy; Photosensitizing Agents; Primary Neoplasm; Process; Prostatic Neoplasms; Proteins; Protocols documentation; Rattus; Reaction; Research; Research Personnel; Safety; Sales; Sampling; Series; Signal Transduction; Singlet Oxygen; Skin; Small Business Innovation Research Grant; Solutions; Study Section; System; Testing; Time; Treatment outcome; United States National Institutes of Health; Validation; Vendor; Visible Radiation; Work; aqueous; base; cancer cell; cancer therapy; clinical application; college; commercialization; data acquisition; design; detector; dosimetry; human subject; improved; in vivo; interest; killings; light intensity; meetings; next generation; physical science; pre-clinical; preclinical study; prognostic; programs; prototype; research study; sensor; success; tool; tumor; usability

DESCRIPTION (provided by applicant): Photodynamic therapy (PDT) is a relatively new, rapidly developing, and promising modality for cancer treatment. PDT uses certain compounds known as photosensitizers (PS's) that are preferentially retained in malignant tumors. With visible light, the photosensitizers initiate a reaction that selectively kills the malignant cells to which they are attached. FDA approval has been granted for treatment of esophageal and certain lung cancers. PDT is being used in clinical trials for bladder, brain, skin and other cancers. PDT is also being applied to important areas outside of cancer treatment including age related macular degeneration and actinic keratosis, a pre-cancerous skin condition. There is considerable evidence that singlet molecular oxygen (O2(a1?)) is the active species in cancer cell necrosis. A real-time dosimeter for singlet oxygen produced during PDT would be a valuable tool for better understanding the PDT process and for improving treatment outcomes. The overall objective of the proposed SBIR Fast Track program is to build upon our recent success in developing a prototype, real-time detector for singlet oxygen to complete focused, but extensive pre-clinical studies. In Phase I we will significantly improve the sensitivity of the sensor and quantitatively demonstrate these improvements in a series of in-vitro and in-vivo studies. In Phase II we will incorporate the lessons learned in Phase I and build an upgraded, fieldable version and deliver it to the Massachusetts General Hospital (MGH) for an extensive series of animal and human studies. One critical study will be to demonstrate the quantitative relationship between PDT treated tumor regression and the amount of singlet oxygen produced during the treatment. Carefully constructed protocols for the animal studies will examine important PDT parameters including PS type and concentration, light intensity and total dose, and the time between PS infusion and PDT treatment. These studies will use only FDA approved photosensitizers (ALA and BPD) to maximize the relevance of the results to PDT in humans. Near the end of the three year program, MGH will complete a study of PDT generated singlet oxygen from healthy human subjects with topical ALA on their skin. The Fast Track program will result in a robust and statistically significant data base that will be submitted to the FDA at the end of the program. The goal is to obtain FDA approval to market the singlet oxygen monitor to PDT researchers as the initial target market. This program will be relevant to an emerging form of cancer therapy and will provide validation of a real-time sensor that has the potential to improve PDT treatment outcomes. PDT is a growing and promising modality, and the results of this project will not only provide important data that could improve treatment outcomes, but also facilitate FDA approval of the device so it would be available to more researchers with the goal of advancing PDT.

描述（由申请人提供）：光动力疗法（PDT）是一种相对较新、发展迅速且有前途的癌症治疗方法。PDT使用某些被称为光敏剂（PS）的化合物，这些化合物优先保留在恶性肿瘤中。在可见光下，光敏剂引发一种反应，选择性地杀死它们所附着的恶性细胞。FDA已批准用于治疗食管癌和某些肺癌。PDT正用于膀胱癌、脑癌、皮肤癌和其他癌症的临床试验。PDT也被应用于癌症治疗以外的重要领域，包括年龄相关性黄斑变性和光化性角化病，一种癌前皮肤病。有相当多的证据表明，单线态分子氧（O2（a1？））是癌细胞坏死的活性物质PDT过程中产生的单线态氧的实时剂量计将是更好地理解PDT过程和改善治疗结果的有价值的工具。SBIR快速通道计划的总体目标是建立在我们最近成功开发单线态氧实时检测器原型的基础上，以完成集中但广泛的临床前研究。在第一阶段，我们将显著提高传感器的灵敏度，并在一系列体外和体内研究中定量证明这些改进。在第二阶段，我们将结合第一阶段的经验教训，建立一个升级的，可现场使用的版本，并将其交付给马萨诸塞州总医院（MGH）进行一系列广泛的动物和人体研究。一项关键的研究将是证明PDT治疗的肿瘤消退与治疗期间产生的单线态氧的量之间的定量关系。精心构建的动物研究方案将检查重要的PDT参数，包括PS类型和浓度，光强度和总剂量，以及PS输注和PDT治疗之间的时间。这些研究将仅使用FDA批准的光敏剂（ALA和BPD），以最大限度地提高结果与人体PDT的相关性。在三年计划接近尾声时，MGH将完成一项PDT产生单线态氧的研究，该研究来自皮肤上有局部ALA的健康人类受试者。快速通道项目将产生一个强大的、具有统计学意义的数据库，并将在项目结束时提交给FDA。我们的目标是获得FDA批准，将单线态氧监测器作为最初的目标市场销售给PDT研究人员。该计划将与新兴的癌症治疗形式相关，并将提供实时传感器的验证，该传感器有可能改善PDT治疗结果。PDT是一种不断发展和有前途的方式，该项目的结果不仅将提供可以改善治疗结果的重要数据，而且还将促进FDA批准该设备，以便更多的研究人员可以使用该设备来推进PDT。