Fluorine magnetic resonance imaging (19F MRI) using polymer tracers overcomes limitations of conventional proton MRI by offering enhanced specificity. However, the lack of systematic comparisons among fluorinated polymers has hindered rational tracer design. In this study, we synthesized an extensive library of water-soluble fluorinated copolymers by varying ratios of hydrophilic and fluorinated monomers and evaluated their 19F MRI properties to identify key structure-property relationships. Optimizing the hydrophilicity of the non-fluorinated comonomer increased fluorine content without compromising water solubility, thereby enhancing the MRI signal. Factors such as chemical structure, molecular interactions, and magnetic relaxation times also significantly influenced tracer performance. The optimized copolymer, poly((N-(2,2,2-trifluoroethyl)acrylamide)60-stat-(N-(2-hydroxyethyl)acrylamide)40), exhibited unprecedented 19F MRI sensitivity with detection limits below 1 mg mL-1, the highest reported to date. We demonstrated the tracer's potential through successful in vivo 19F MRI visualization of solid tumors in mouse models, highlighting its promise for advanced biomedical imaging applications.

Department of Chemistry and Physics of Surfaces and Interfaces Institute of Macromolecular Chemistry AS CR Prague 6 162 06 Czech Republic

Department of Diagnostic and Interventional Radiology Institute for Clinical and Experimental Medicine Prague 4 140 21 Czech Republic

Department of Physical and Macromolecular Chemistry Faculty of Science Charles University Prague 2 128 00 Czech Republic

Faculty of Health Studies Technical University of Liberec Liberec 461 17 Czech Republic

Institute of Biophysics and Informatics 1st Faculty of Medicine Charles University Prague 2 Prague 128 00 Czech Republic

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