A Multifunctional Contrast Agent for ¹⁹F-Based Magnetic Resonance Imaging

Magnetic resonance imaging, MRI, relying on ¹⁹F nuclei has attracted much attention, because the isotopes exhibit a high gyromagnetic ratio (comparable to that of protons) and have 100% natural abundance. Furthermore, due to the very low traces of intrinsic fluorine in biological tissues, fluorine labeling allows easy visualization in vivo using ¹⁹F-based MRI. However, one of the drawbacks of the available fluorine tracers is their very limited solubility in water. Here, we detail the design and preparation of a set of water-compatible fluorine-rich polymers as contrast agents that can enhance the effectiveness of ¹⁹F-based MRI. The agents are synthesized using the nucleophilic addition reaction between poly(isobutylene-alt-maleic anhydride) copolymer and a mixture of amine-appended fluorine groups and polyethylene glycol (PEG) blocks. This allows control over the polymer architecture and stoichiometry, resulting in good affinity to water solutions. We further investigate the effects of introducing additional segmental mobility to the fluorine moieties in the polymer, by inserting a PEG linker between the moieties and the polymer backbone. We find that controlling the polymer stoichiometry and introducing additional segmental mobility enhance the NMR signals and narrow the peak profile. In particular, we assess the impact of the PEG linker on T₂* and T₁ relaxation times, using a series of gradient-recalled echo images with varying echo times, TE, or recovery time, TR, respectively. We find that for equivalent concentrations, the PEG linker greatly increases T₂*, while maintaining high T₁ values, as compared to polymers without this linker. Phantom images collected from these compounds show bright signals over a background with high intensities.