Design and Synthesis of Fluorinated Amphiphile as 19F MRI/Fluorescence Dual-Imaging Agent by Tuning the Self-Assembly

Both F-19 MRI and optical imaging are powerful noninvasive molecular imaging modalities in biomedical applications. To integrate these two complementary imaging modalities, the design and synthesis of a novel F-19 MRI/fluorescence dual-modal imaging agent is reported herein. Through Sonogashira coupling reaction between the fluorinated phenylacetylene and 1,2,4,5-tetraiodobenzene, a fluorophore with 48 symmetrical fluorines at its periphery was constructed with high efficacy. High aqueous solubility was achieved by PEGylation of the fluorophore with monodisperse PEGs. However, an unexpected self-assembly of the PEGylated amphiphilic fluorophore in water "turned off" the F-19 NMR signal. However, hydrogenation of the triple bonds or introduction of branched monodisperse PEGs was able to efficiently tune the self-assembly, resulting in the "turning on" of the F-19 NMR signal. One of these amphiphiles combines the advantages of label-free fluorescence, high F-19 MRI sensitivity, biocompatibility, and excellent aqueous solubility. The results demonstrate the great potential of such amphiphiles for real-time F-19 MRI and fluorescence dual-modality imaging.