Minimally invasive quantitative tissue oxygen sensors to personalize cancer care

项目摘要和摘要 低氧(耗氧型)肿瘤对包括放射治疗在内的治疗更具抵抗力。这一趋势已经 已经在包括前列腺癌、头颈部和宫颈癌在内的多种癌症中被发现。放射生物学 研究表明，增加辐射剂量可以用来克服缺氧诱导的抵抗力和 在含氧量更高的环境中达到与较低剂量相同的效果。少校 实施这种(和其他)低氧靶向疗法的障碍是缺乏合适的氧气传感器。 可操作的氧气传感器应该是定量的、与工作流程兼容的，并为每个传感器提供空间背景 测量。目前和过去的氧气传感替代方案要么是定性的，要么是过于侵入性的，或者两者兼而有之。这个 提出的氧气传感器将提供一种与工作流程兼容的方法来获得定量的肿瘤氧气数据。这个 传感器是使用MRI非侵入性测量的，它提供了每个传感器的空间/解剖环境 测量。该传感器完全由硅胶制成，以微创的方式插入，平衡 与周围组织迅速结合，且完全可逆。材料的聚合性使其能够保持 无限期地放置在插入部位，以便能够进行长期监测。拟议的工作重点是选择一个 铅配方(目标1)，在小动物肿瘤模型中的评价(目标2)，以及在大动物中的评价 模拟人体使用过程中预期的组织体积的模型(目标3)。作为这件事的一部分而生产的传感器 该提案将可翻译为肿瘤学的其他应用程序，但也可翻译为非肿瘤学应用程序 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.