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  19 F-MRI raises the need to further enhance this platform's capabilities. Here, we employ the principles of CEST-MRI in  19 F-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  19 F-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  19 F-MRI to the mapping of targets that have so-far remained non-detectable.