Partially Fluorinated Copolymers as Oxygen Sensitive 19 F MRI Agents

• Published in: Chemistry : a European journal Vol. 26; no. 44; pp. 9982 - 9990
• Main Authors: Taylor, Nicholas G, Chung, Sang Hun, Kwansa, Albert L, Johnson, 3rd, Rob R, Teator, Aaron J, Milliken, Nina J B, Koshlap, Karl M, Yingling, Yaroslava G, Lee, Yueh Z, Leibfarth, Frank A
• Format: Journal Article
• Language: English
• Published: Germany 06.08.2020
• Subjects: Fluorine - analysis; Fluorine - chemistry; Halogenation; Magnetic Resonance Imaging; Oxygen - analysis; Oxygen - chemistry; Partial Pressure; Polymers - chemistry; 19F MRI; amphiphilic copolymer; oxygen sensing; fluorinated monomers; polyacrylates
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.202001505

Effective diagnosis of disease and its progression can be aided by F magnetic resonance imaging (MRI) techniques. Specifically, the inherent sensitivity of the spin-lattice relaxation time (T ) of F nuclei to oxygen partial pressure makes 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 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 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 F MRI. The highest-performing material composition demonstrated a signal-to-noise ratio that corresponded to an apparent F density of 220 mm, which surpasses the threshold of 126 mm F required for visualization on a three Tesla clinical MRI. Furthermore, the T of these high performing materials demonstrated a linear relationship with solution oxygenation, with oxygen sensitivity reaching 240×10  mmHg s . The relationships between material composition and F MRI performance identified herein suggest general structure-property criteria for the further improvement of modular, water-soluble F MRI agents for quantifying oxygenation in environments relevant to medical imaging.