Single Fluorinated Agent for Multiplexed ¹⁹F-MRI with Micromolar Detectability Based on Dynamic Exchange

The weak thermal polarization of nuclear spins limits the sensitivity of MRI, even for MR-sensitive nuclei as fluorine-19. Therefore, despite being the source of inspiration for the development of background-free MRI for various applications, including for multiplexed imaging, the inability to map very low concentrations of targets using ¹⁹F-MRI raises the need to further enhance this platform's capabilities. Here, we employ the principles of CEST-MRI in ¹⁹F-MRI to obtain a 900-fold signal amplification of a biocompatible fluorinated agent, which can be presented in a “multicolor” fashion. Capitalizing on the dynamic interactions in host–guest supramolecular assemblies in an approach termed GEST, we demonstrate that an inhalable fluorinated anesthetic can be used as a single ¹⁹F-probe for the concurrent detection of micromolar levels of two targets, with potential in vivo translatability. Further extending GEST with new designs could expand the applicability of ¹⁹F-MRI to the mapping of targets that have so-far remained non-detectable.