Sensitive Multichannel 19F Magnetic Resonance Imaging Enabled by Paramagnetic Fluorinated Ionic Liquid-Based Probes

Owing to its negligible biological background and high magnetic resonance sensitivity, F-19 magnetic resonance imaging (MRI) has emerged as a competitive complement for H-1 MRI, which is already widely used in biomedical research and clinical practice. The performance of F-19 MRI is greatly reliant on imaging probes, the development of which poses considerable demands on F-19 sources. Fluorinated ionic liquids (FILs) have recently attracted increasing attention as alternative F-19 sources because of their good aqueous solubility, ease of chemical modification, and high fluorine contents. However, the imaging performance of FIL-based probes is significantly restricted by their unfavorable F-19 relaxation times. Herein, we developed a strategy to modulate the F-19 relaxation times (including both T-1 and T-2) of FILs by exploiting the paramagnetic relaxation enhancement effect of Mn2+ ions to promote their imaging capacity. The F-19 relaxation times of three FILs including EMIMBF4, BMIMOTf, and BMIMPF6 are appropriately tuned with paramagnetic Mn2+ ions at optimized concentrations, resulting in significant signal enhancement over 5-fold. We further utilized liposils to encapsulate these FILs with Mn2+ ions to construct F-19 MRI probes, which enables fast and clear F-19 MRI as illustrated by a series of in vivo experiments. Moreover, we made a F-19 MRI probe containing all three FILs and Mn2+ ions at the optimized concentration, whose capacity for multiplexed F-19 MRI is also validated with in vivo experiments. Our study demonstrates the promising potential of paramagnetic FIL-based probes for in vivo "hot spot" F-19 MRI, and more importantly, the feasibility of relaxation modulation for the construction of high-performance F-19 MRI probes.