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

Automated summary

By applying the principles of CEST-MRI to F-19-MRI, researchers achieved a 900-fold signal amplification for a biocompatible fluorinated agent and demonstrated the potential for using an inhalable fluorinated anesthetic as a single F-19 probe to detect two targets simultaneously in host-guest supramolecular assemblies. Further advancements in this approach could expand the applicability of F-19-MRI to previously undetectable targets.