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: 7272152
• 负责人: STEVEN J DAVIS
• 金额: $ 15万
• 依托单位: PHYSICAL SCIENCES, INC
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7272152
• 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; Compatible; Computer software; Condition; Coupled; Data; Databases; Detection; Development; Device Approval; Devices; Discrimination; Disease regression; Dose; Effectiveness; Elements; Esophageal; Evaluation; 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; Numbers; 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; Purpose; Range; Rattus; Reaction; Research; Research Personnel; Safety; Sales; Sampling; Score; Series; Signal Transduction; Singlet Oxygen; Skin; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Solutions; Statistically Significant; Study Section; System; Testing; Time; Treatment outcome; United States Food and Drug Administration; 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 study; human subject; improved; in vivo; interest; killings; light intensity; 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）是一种相对较新的，迅速发展的癌症治疗方式。 PDT使用某些称为光敏剂（PS）的化合物优先保留在恶性肿瘤中。使用可见光，光敏剂启动了一种反应，该反应有选择地杀死其附着的恶性细胞。已批准FDA用于治疗食管和某些肺癌。 PDT用于膀胱，脑，皮肤和其他癌症的临床试验中。 PDT还应用于癌症治疗以外的重要领域，包括与年龄相关的黄斑变性和放光性角化病，这是一种癌前的皮肤状况。有大量证据表明，单线分子氧（O2（A1？））是癌细胞坏死中的活性物种。 PDT期间生产的单线氧的实时剂量表将是更好地了解PDT过程并改善治疗结果的宝贵工具。拟议的SBIR快速轨道计划的总体目标是基于我们最近在开发原型，实时探测器的成功方面的成功，从而使单线氧的实时检测器完整专注但广泛的临床前研究。在第一阶段，我们将显着提高传感器的灵敏度，并在一系列体外和体内研究中进行定量证明这些改善。在第二阶段，我们将在第一阶段学习的经验教训，并建立一个升级的现场版本，并将其交付给马萨诸塞州综合医院（MGH）进行一系列广泛的动物和人类研究。一项关键研究将是证明PDT处理过的肿瘤消退与治疗过程中产生的单线氧的数量之间的定量关系。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处理之间的时间。这些研究将仅使用FDA批准的光敏剂（ALA和BPD）来最大程度地提高结果与人类PDT的相关性。在三年计划结束时，MGH将完成对健康受试者的PDT产生的单线氧的研究，其皮肤上有局部ALA。快速跟踪程序将导致稳健且具有统计学意义的数据库，该数据库将在程序结束时提交给FDA。目的是获得FDA批准，以将单线氧监测器推销给PDT研究人员作为初始目标市场。该程序将与新兴形式的癌症治疗相关，并将提供有可能改善PDT治疗结果的实时传感器的验证。 PDT是一种增长且有希望的方式，该项目的结果不仅可以提供可以改善治疗结果的重要数据，而且还可以促进FDA的批准，因此可以向更多的研究人员使用，以推进PDT。