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

Abstract

The combination of the two complementary imaging modalities (19) F 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 (19) F 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 (19) F 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.

Aza-BODIPY Platform: Toward an Efficient Water-Soluble Bimodal Imaging Probe for MRI and Near-Infrared Fluorescence

“…In order to gain more insight into the parameters governing relaxivity, 17 Figure 6. The reduced 17 O transverse relaxation rates first increase (up to ca.…”

“…In order to gain more insight into the parameters governing relaxivity, 17 Figure 6. The reduced 17 O transverse relaxation rates first increase (up to ca. 318 K), then decrease with increasing temperature indicating that the complex is in the slow kinetic region at low temperatures and in the fast exchange region at higher temperatures.…”

“…However small molecular bimodal agents were also reported and proved to be very effective. These agents combine fluorine atoms for 19 F MRI or one, two, or more complexes, which are active in MRI, such as Mn 2+ or Gd 3+ complexes, and one fluorophore, which can be a dipyridophenazine, fluorescein, cyanine, rhodamine, quinoline, BODIPY... [10][11][12][13][14][15][16][17][18] For in vivo optical imaging applications, the fluorophores need to absorb and emit in the spectral range, where biological tissues are more transparent and less scattering. This region, often called biological, transparency or theranostic window, corresponds to near infrared (NIR, as example NIR I corresponds to 650-900 nm).…”

BODIPY Dyes Bearing Multibranched Fluorinated Chains: Synthesis, Structural, and Spectroscopic Studies

“…In particular, the combination of 19 F‐MRI with fluorescence imaging (FLI) allows simultaneously in vivo tracking ( 19 F‐MRI/FLI) and ex vivo intracellular localization (FLI); thus providing in‐depth in vivo detection, higher sensitivity, and real‐time responses . Accordingly, the integration of typical characteristics of an efficient 19 F‐MRI contrast agent, that is, an appropriate number of magnetically equivalent fluorine atoms in the BODIPY core, would result in an efficient dual modality ( 19 F‐MRI/FLI) imaging agent . Despite the massive amount of work aimed at the structural variation of BODIPY cores, only a few examples of fluorinated BODIPYs have been reported in the literature, to date, and most of them are characterized by a low number of fluorine atoms .…”

“…[11b,c] Accordingly,t he integration of typical characteristics of an efficient 19 F-MRI contrast agent, that is, an appropriate number of magnetically equivalent fluorine atoms in the BODIPY core, would result in an efficient dual modality ( 19 F-MRI/FLI) imaging agent. [12] Despitet he massive amount of work aimed at the structuralv ariation of BODIPY cores, only a few examples of fluorinated BODIPYs have been reported in the literature, to date, and most of them are characterized by a low number of fluorinea toms. [13] This might be due to the environmental impact of perfluorinated compounds with linear chains longer than six carbon atoms, [14] although alternatives have been recently provided by using multibranched fluorinated compounds with ultrashort fluorinated alkyl groups.…”