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

Abstract

In this study, an original aza-BODIPY system comprising two Gd 3+ complexes has been designed and synthesized for magnetic resonance imaging/optical imaging application, by functionalization of the boron center. This strategy enabled to obtain a positively-charged bimodal probe, which displays an increased water-solubility, optimized photophysical properties in the near-infrared region, and very promising relaxometric properties. The absorption and emission wavelengths are 705 and 741 nm respectively, with a quantum yield of around 10 % in aqueous media. Moreover, the system does not produce singlet oxygen upon excitation, which would be toxic for tissues. The relaxivity obtained is high at intermediate fields (16.1 mM-1 .s-1 at 20 MHz and 310 K) and competes with that of bigger or more rigid systems. A full relaxometric and 17 O NMR study and fitting of the data using the Lipari-Szabo approach showed that this high relaxivity can be explained by the size of the system and the presence of some small aggregates. These optimized photophysical and relaxometric properties highlight the potential use of such systems for future bimodal imaging studies.

Aza-BODIPY: A New Vector for Enhanced Theranostic Boron Neutron Capture Therapy Applications

“…In particular, we used B-functionalized aza-BODIPYs (Figure 1b,c), as they have numerous advantages, such as a very high chemical and photochemical photostability, and excellent photophysical properties, rendering them suitable fluorophore for the NIR-I to the SWIR region (Figure 1d). Previously, we developed a strategy, which favored their solubilization and limited their aggregation in biologically relevant media (i.e., water, PBS, or serum), by substituting the fluorine atoms on the boron by alkyne ammonium groups [34,35,48]. Very recently, we used this strategy on a particular Donor-Acceptor-Donor' aza-BODIPY structure, which emits in the SWIR region, yielding a water-soluble derivative SWIR-WAZABY-01 (See the ESI and Reference [29]; WAZABY for Water-Soluble aza-BODIPY).…”

“…Among the different optical probes, boron-dipyrromethene dyes (BODIPYs, Figure 1a) are very versatile organic fluorophores with tunable optical properties from the visible to the NIR-I (Near Infrared) and SWIR (Short Wave Infrared) optical windows [27][28][29], which display excellent photophysical properties controlled by substitution pattern conferring a strong interest for these compounds as theranostic tools [30,31]. Moreover, the fluorine atoms on the boron could be substituted by acetylides bearing ammonium groups for engrafting functional groups to increase the water-solubility and to conjugate them with chelates for OI/PET, OI/SPECT bimodal imaging [32][33][34][35], and therapeutic moieties [31,36,37]. BODIPY fluorophores are also interesting for BNCT, as they possess a boron atom.…”

“…To bridge this gap, we decided to tether a 10 B-BSH on a NIR-emitting BODIPY derivative named aza-BODIPY ( Figure 1b), thereby creating a theranostic system gathering the advantages of both aza-BODIPY and 10 B-BSH components. media (i.e., water, PBS, or serum), by substituting the fluorine atoms on the boron by alkyne ammonium groups [34,35,48]. Very recently, we used this strategy on a particular Donor-Acceptor-Donor' aza-BODIPY structure, which emits in the SWIR region, yielding a water-soluble derivative SWIR-WAZABY-01 (See the ESI and Reference [29]; WAZABY for Water-Soluble aza-BODIPY).…”

Fluorine-18-Labeled Fluorescent Dyes for Dual-Mode Molecular Imaging

“…One drawback of BODIPY dyes is their low Stokes shifts (usually below 1000 cm −1 ), reducing signal-to-background ratio due to reabsorption and use of narrow filters. Nowadays, biomedical applications of BODIPY dyes are mainly focused on cellular imaging and sensing, however, examples of NIRF OPI and photoacoustic imaging (PAI) have been described [53,54]. Given the importance of BODIPY dyes as fluorescent probes, several groups have been involved in the development of dual-mode imaging agents including OPI-PET, OPI-SPECT, or OPI-MRI [53,55,56].…”

“…Nowadays, biomedical applications of BODIPY dyes are mainly focused on cellular imaging and sensing, however, examples of NIRF OPI and photoacoustic imaging (PAI) have been described [53,54]. Given the importance of BODIPY dyes as fluorescent probes, several groups have been involved in the development of dual-mode imaging agents including OPI-PET, OPI-SPECT, or OPI-MRI [53,55,56]. Recently, Ali et al published an overview of radiolabeled BODIPYs in the literature including 125 I, 111 In, and 89 Zr adducts [57].…”