Minimally invasive quantitative tissue oxygen sensors to personalize cancer care

项目概要和摘要 缺氧（缺氧）肿瘤对包括放射治疗在内的治疗更具抵抗力。这一趋势 在包括前列腺癌、头颈癌和宫颈癌在内的多种癌症中均可见。放射生物 研究表明，提高辐射剂量可用于克服缺氧诱导的抗性， 在氧合较好的环境中，达到与较低剂量相同的有效性水平。主要 实施这种（和其它）低氧靶向治疗的障碍是缺乏合适的氧传感器。 可操作的氧传感器应该是定量的，工作流程兼容的，并为每个传感器提供空间背景。 测量.当前和过去的氧气传感替代方案要么是定性的，要么是侵入性太强，要么两者兼而有之。的 所提出的氧传感器将提供工作流兼容的方法来获得定量肿瘤氧数据。的 使用MRI对传感器进行非侵入性测量，MRI为每个传感器提供空间/解剖背景 测量.传感器完全由硅胶制成，采用微创方法插入， 与周围组织迅速接触，并且完全可逆。材料的聚合性质使其能够保持 在插入部位无限期地进行，以实现长期监测。拟议的工作重点是选择一个 先导制剂（目标1）、在小动物肿瘤模型中评价（目标2）和在大动物中评价 模型，以模拟人体使用期间预期的组织体积（目标3）。作为这一部分生产的传感器 该提案将可转化为肿瘤学的其他应用，但也可转化为非肿瘤学应用 包括组织健康和创伤。

Project Summary and Abstract Hypoxic (oxygen depleted) tumors are more resistant to treatments including radiation therapy. This trend has been seen across a wide range of cancers including prostate, head and neck, and cervical. Radiobiological studies have shown that elevated radiation doses can be used to overcome hypoxia-induced resistance and achieve the same level of effectiveness as lower doses in more well-oxygenated environments. The major impediment to implementing this (and other) hypoxia targeting therapies is the lack of a suitable oxygen sensor. Actionable oxygen sensors should be quantitative, workflow compatible, and provide spatial context for each measurement. Current and past alternatives for oxygen sensing are either qualitative, too invasive, or both. The proposed oxygen sensor will offer a workflow-compatible method to obtain quantitative tumor oxygen data. The sensor is measured non-invasively using MRI which provides a spatial/anatomical context for each measurement. The sensor is made completely of silicone, inserted with minimally invasive methods, equilibrates quickly with the surrounding tissue, and is fully reversible. The polymeric nature of the material allows it to remain at the site of insertion indefinitely to enable long-term monitoring. The proposed work focuses on selection of a lead formulation (Aim 1), evaluation in a small animal tumor model (Aim 2), and evaluation in a large animal model to mimic the tissue volumes expected during human use (Aim 3). The sensor produced as part of this proposal will be translatable to additional applications in oncology, but also to non-oncology applications including tissue health and trauma.