Elucidating the Impact of Hydrophilic Segments on ¹⁹F MRI Sensitivity of Fluorinated Block Copolymers

A major challenge in the preparation of polymeric ¹⁹F magnetic resonance imaging (MRI) contrast agents (CAs) is signal attenuation caused by reduced segmental mobility of partly fluorinated polymers possessing large numbers of fluorine atoms. Previous studies have thus mainly focused on the development of fluorinated segments for improved ¹⁹F MRI; however, detailed investigations of the role of hydrophilic segments on imaging performance remain scarce. In this study, three hydrophilic and biocompatible monomers, i.e., 2-(methylsulfinyl)ethyl acrylate (MSEA), oligo(ethylene glycol) methyl ether acrylate (OEGA), and oligo(2-methyl-2-oxazoline) acrylate (OMOXA), were used to prepare perfluoropolyether (PFPE)-containing amphiphilic block polymers through reversible addition-fragmentation chain-transfer (RAFT) polymerization. The effect of the different hydrophilic segments on ¹⁹F imaging performance was explored. The three polymers could be readily dissolved in aqueous solutions, forming assemblies with the hydrophobic PFPE as the core and the hydrophilic chains as the shell. Molecular dynamics simulations demonstrate that the POMOXA chains adopt a rigid, extended conformation, leading to a relatively short ¹⁹F NMR spin-spin relaxation time (T₂), lower NMR detectable ¹⁹F spins (i.e., visibility), and the least intense ¹⁹F MRI signal. In contrast, although PMSEA-PFPE has a shorter ¹⁹F NMR T₂ than POEGA-PFPE, the much higher ¹⁹F spin visibility enhances its MRI signal intensity. The result confirms the importance of maintaining both high fluorine visibility and long T₂ relaxation time to prepare effective CAs and highlight the key role of the nonfluorinated hydrophilic segments in determining these parameters.