Partially Fluorinated Copolymers as Oxygen Sensitive ¹⁹ F MRI Agents

Effective diagnosis of disease and its progression can be aided by ¹⁹ F magnetic resonance imaging (MRI) techniques. Specifically, the inherent sensitivity of the spin-lattice relaxation time (T₁ ) of ¹⁹ F nuclei to oxygen partial pressure makes ¹⁹ F MRI an attractive non-invasive approach to quantify tissue oxygenation in a spatiotemporal manner. However, there are only few materials with the adequate sensitivity to be used as oxygen-sensitive ¹⁹ F MRI agents at clinically relevant field strengths. Motivated by the limitations in current technologies, we report highly fluorinated monomers that provide a platform approach to realize water-soluble, partially fluorinated copolymers as ¹⁹ F MRI agents with the required sensitivity to quantify solution oxygenation at clinically relevant magnetic field strengths. The synthesis of a systematic library of partially fluorinated copolymers enabled a comprehensive evaluation of copolymer structure-property relationships relevant to ¹⁹ F MRI. The highest-performing material composition demonstrated a signal-to-noise ratio that corresponded to an apparent ¹⁹ F density of 220 mm, which surpasses the threshold of 126 mm ¹⁹ F required for visualization on a three Tesla clinical MRI. Furthermore, the T₁ of these high performing materials demonstrated a linear relationship with solution oxygenation, with oxygen sensitivity reaching 240×10^-5  mmHg^-1 s^-1 . The relationships between material composition and ¹⁹ F MRI performance identified herein suggest general structure-property criteria for the further improvement of modular, water-soluble ¹⁹ F MRI agents for quantifying oxygenation in environments relevant to medical imaging.