Fluorinated Water-Soluble Poly(2-oxazoline)s as Highly Sensitive ¹⁹F MRI Contrast Agents

Abstract

Recently, 19F magnetic resonance imaging (MRI) emerged as a powerful noninvasive diagnostic tool in modern medicine. Fluorinated polymer materials represent an attractive class of MRI contrast agents (CAs) due to their structural variability and tunable properties. Herein, we describe for the first time the 19F MRI of CAs based on fluorinated water-soluble poly(2-oxazoline)s (PAOx), a polymer class with increasing popularity in biomedical sciences. A series of fluorinated PAOx with increasing fluorine content were synthesized by controlled side-chain hydrolysis of poly(2-methyl-2-oxazoline) followed by reacylation of its ethylenimine units by difluoroacetic anhydride. As the increasing fluorine content leads to the copolymer hydrophobization, their composition was optimized for maximal 19F MRI performance while retaining good solubility in water. The magnetic properties of the water-soluble polymers were studied in vitro by 19F NMR and MRI, revealing their outstanding relaxation properties and imaging sensitivity. All CAs were found to be noncytotoxic for HeLa cells in vitro. Finally, the diagnostic potential of the new CAs was demonstrated by a successful in vivo 19F MRI visualization of the selected fluorinated polymer in rats.