Partially Fluorinated Copolymers as Oxygen Sensitive <sup>19</sup>F MRI Agents
Nicholas G. Taylor, Sang Hun Chung, Albert L. Kwansa, Rob R. Johnson, Aaron J. Teator, Nina J. B. Milliken, Karl M. Koshlap, Yaroslava G. Yingling, Yueh Z. Lee, Frank A. Leibfarth
Abstract
Abstract 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 ( T 1 ) 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 m m , which surpasses the threshold of 126 m m 19 F required for visualization on a three Tesla clinical MRI. Furthermore, the T 1 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.