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

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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.