FY20 SBIR PHASE 1 TOPIC #400 - TDA RADI-SENSE: ENCAPSULATED NANOPARTICLE OXYGEN IMAGING AGENTS FOR RADIOTHERAPY GUIDANCE

辐射剂量效应在很大程度上取决于肿瘤部位的氧浓度，由于脉管系统紊乱，氧浓度是可变的。肿瘤的低氧合区域与氧合良好的区域相比需要更高的辐射剂量。顺磁探针是氧敏感的，并且探针线宽和弛豫时间可以根据O2浓度和分压进行校准。在动物模型中，已经显示这些探针可以识别缺氧肿瘤区域。选择性靶向缺氧区域（通过EPR成像识别）已被证明可以提高临床前工作中的存活率。 目前尚无FDA批准的可直接注射的人用顺磁性成像剂。存在许多FDA批准的生物相容性、透气性聚合物，其可用于将身体环境与成像剂环境分离，同时仍保持氧敏感性。在包封之前将成像剂共价包封到无机纳米颗粒载体上进一步确保了它们与身体环境的长期分离。 在这个项目中，我们将创建一个成像剂包裹在一个生物相容性，但透气性聚合物。将在小鼠模型中对包封和游离探针进行体内并排比较，以证明氧敏感性得到保留。

Radiation dose effect is heavily dependent on the oxygen concentration at the tumor site, which is variable due to disorganized vasculature. Hypoxic regions of tumors require a higher radiation dose compared to well oxygenated regions. Paramagnetic probes are oxygen sensitive and probe linewidth and relaxation time can be calibrated to O2 concentration and partial pressure. In animal models it has been shown these probes can identify hypoxic tumor regions. Selectively targeting hypoxic regions (identified by EPR imaging) has been shown to improve survivability in pre-clinical work. There are no FDA cleared directly injectable paramagnetic imaging agents for human use. A number of FDA cleared biocompatible, gas permeable polymers exist which could be used to separate the body environment from the imaging agent environment, while still retaining the oxygen sensitivity. Anchoring the imaging agents covalently onto an inorganic nanoparticle carrier prior to encapsulation further ensures their long-term separation from the body environment. In this project we will create an imaging agent encased in a biocompatible but gas permeable polymer. An in vivo side by side comparison in a mouse model will be made between encapsulated and free probe to demonstrate that oxygen sensitivity has been retained.