Small BODIPY Probes for Combined Dual 19F MRI and Fluorescence Imaging

The combination of the two complementary imaging modalities ¹⁹F magnetic resonance imaging (MRI) and fluorescence imaging (FLI) possesses high potential for biological and medical applications. Herein we report the first design, synthesis, dual detection validation, and cytotoxic testing of four promising BODIPY dyes for dual ¹⁹F MRI–fluorescence detection. Using straightforward Steglich reactions, small fluorinated alcohols were easily covalently tethered to a BODIPY dye in high yields, leaving its fluorescence properties unaffected. The synthesized compounds were analyzed with various techniques to demonstrate their potential utility in dual imaging. As expected, the chemically and magnetically equivalent trifluoromethyl groups of the agents exhibited a single NMR signal. The determined longitudinal relaxation times T₁ and the transverse relaxation times T₂, both in the lower second range, enabled the imaging of four compounds in vitro. The most auspicious dual ¹⁹F MRI–fluorescence agent was also successfully imaged in a mouse post‐mortem within a 9.4 T small‐animal tomograph. Toxicological assays with human cells (primary HUVEC and HepG2 cell line) also indicated the possibility for animal testing.