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依赖于肿瘤部位的氧浓度，而氧浓度是由于血管系统紊乱而变化的。与氧合良好的肿瘤相比，肿瘤的缺氧区需要更高的辐射剂量。顺磁探头是氧敏感的，探针线宽和弛豫时间可以根据氧气浓度和分压进行校准。在动物模型中，已经证明这些探针可以识别缺氧性肿瘤区域。选择性靶向缺氧区(通过EPR成像识别)已被证明在临床前工作中可以提高存活率。 目前还没有FDA批准的可直接注射的人类使用的顺磁显像剂。FDA批准的许多生物相容性、透气性聚合物可用于将人体环境与显像剂环境分开，同时仍保持对氧的敏感性。在封装前将成像剂共价锚定在无机纳米颗粒载体上，进一步确保了它们与人体环境的长期分离。 在这个项目中，我们将创建一种包裹在生物兼容但可透气的聚合物中的显像剂。在小鼠模型中，将在体内对包裹和游离探针进行并排比较，以证明氧的敏感性得到了保留。

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.