Optimizing cancer photodynamic therapy using photoacoustic lifetime imaging

使用光声寿命成像优化癌症光动力治疗

基本信息

批准号：
8815629
负责人：
Shai Ashkenazi
金额：
$ 31.63万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-12-22 至 2019-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8815629
关键词：
Accounting Address Affect Algorithms Animal Cancer Model Animals Blood Vessels Blood capillaries Blood flow Breathing Cancer Biology Cancer Model Canis familiaris Cell Hypoxia Cells Cessation of life Clinic Clinical Clinical Assessment Tool Clinical Treatment Clinical Trials Collaborations Complex Computers Consumption Dependency Development Dose Drops Dyes Electrodes Environment FDA approved Feedback Felis catus Fiber Optics Foundations Future Gases Gold Head and Neck Cancer Human Hypoxia Image Imaging Techniques In Vitro Injection of therapeutic agent Investigation Lasers Lead Life Light Lighting Localized Malignant Neoplasm Location Malignant Neoplasms Measurement Measures Mediator of activation protein Medical Imaging Methylene blue Modality Modification Molecular Monitor Morbidity - disease rate Mouth Neoplasms Mus Needles Nitrogen Oncologist Oral cavity Outcome Oxygen PUVA Photochemotherapy Patients Penetration Performance Photosensitizing Agents Physicians Physiologic pulse Play Proliferating Radiation therapy Radiosurgery Reading Recurrence Relapse Reporting Research Role Site System Systems Development Techniques Technology Temperature Testing Time Tissues Translating Translations Treatment Efficacy Treatment Protocols Treatment outcome Tumor Oxygenation Ultrasonography Validation Variant Work base cancer diagnosis cancer therapy case-by-case basis chemotherapy clinical application common treatment cost effective data acquisition design head and neck cancer patient image guided image reconstruction imaging agent imaging modality imaging probe imaging system improved in vivo malignant mouth neoplasm minimally invasive non-invasive imaging outcome forecast photoacoustic imaging preclinical study programs public health relevance research study therapy outcome tissue oxygenation tool treatment planning tumor tumor progression

项目摘要

DESCRIPTION (provided by applicant): Head and neck cancers annually account for 3.2% (39,750) of all new cancers and 2.2% (12,460) of all cancer deaths in the US. Approximately 45% of these patients will relapse after primary therapy with surgery and radiation with or without chemotherapy. Recurrences in patients who previously received chemotherapy tend to be more aggressive, with one study reporting a median survival of 107 days. In this proposal we address the urgent need for a minimally invasive, non-toxic, cost-effective, local modality for treating recurrent head and neck cancers with minimal treatment-associated morbidity, which will allow the patient to function as normally as possible in their remaining life-time. We believe this can be achieved by combining Photodynamic therapy (PDT) with photoacoustic lifetime imaging (PALI), a newly developed technique for tissue oxygen imaging. PDT is a light-activated local cancer treatment. Extensive studies during the last 2 decades have established PDT as effective in the treatment of head and neck cancers. However, tissue oxygenation and light penetration strongly affect the efficacy of PDT. We hypothesize that the ability to measure tissue oxygen using PALI, and augmenting its level in the tumor environment will improve the treatment, its outcome and cure rates. Moreover, PALI images will provide a real-time assessment of light penetration to the treated site and the possibility of personalized optimization of PDT light dose. This R01 proposal is based on the results of an on-going R21 project that show feasibility of imaging tissue oxygen in small animals. We will first conduct a comprehensive investigation of the PALI technique in order to accurately characterize its precision and regions of applicability with respect to environmental parameters such as pH and temperature (Aim 1). The scope of the PALI application in an in vivo environment will be tested on small animals (Aim 2). Based on the experimental outcomes, we will develop a portable clinical system for PALI guided PDT treatment (Aim 3). The system will be evaluated in large animal head and neck cancer models. A more extensive study will then be conducted to test the hypothesis that PALI feedback can guide parameter modification (including gas mixture breathing and light dose) on a case-by-case basis, to optimize the efficacy of PDT treatment (Aim 4). Ultimately, we expect the technique to be translated to clinics, significantly improving treatment outcomes of head and neck cancer patients. The results of this project could also drive the development of PALI for other clinical applications, such as guiding chemotherapy and radiotherapy.

描述（由申请人提供）：在美国，头颈癌每年占所有新发癌症的 3.2% (39,750)，占所有癌症死亡的 2.2% (12,460)。这些患者中约 45% 在手术和放疗联合或不联合化疗等主要治疗后会复发。先前接受过化疗的患者的复发往往更具侵袭性，一项研究报告中位生存期为 107 天。在这项提案中，我们迫切需要一种微创、无毒、具有成本效益的局部治疗复发性头颈癌的方法，同时将治疗相关的发病率降至最低，这将使患者能够尽可能正常地生活剩余寿命。我们相信这可以通过将光动力疗法（PDT）与光声寿命成像（PALI）相结合来实现，PALI是一种新开发的组织氧成像技术。 PDT 是一种光激活的局部癌症治疗方法。过去 20 年的广泛研究已证实 PDT 对治疗头颈癌有效。然而，组织氧合和光穿透强烈影响PDT的疗效。我们假设使用 PALI 测量组织氧并提高其在肿瘤环境中的水平的能力将改善治疗、其结果和治愈率。此外，PALI 图像将提供治疗部位光穿透的实时评估以及 PDT 光剂量个性化优化的可能性。该 R01 提案基于正在进行的 R21 项目的结果，该项目显示了对小动物组织氧进行成像的可行性。我们将首先对 PALI 技术进行全面研究，以准确表征其精度以及 pH 和温度等环境参数的适用范围（目标 1）。 PALI 在体内环境中的应用范围将在小动物上进行测试（目标 2）。根据实验结果，我们将开发一种用于 PALI 引导的 PDT 治疗的便携式临床系统（目标 3）。该系统将在大型动物头颈癌模型中进行评估。然后将进行更广泛的研究，以检验 PALI 反馈可以根据具体情况指导参数修改（包括气体混合物呼吸和光剂量）的假设，以优化 PDT 治疗的疗效（目标 4）。最终，我们期望该技术能够转化为临床，显着改善头颈癌患者的治疗结果。该项目的结果还可以推动 PALI 的其他临床应用的发展，例如指导化疗和放疗。