Visualization of Fluoride Ions In Vivo Using a Gadolinium(III)-Coumarin Complex-Based Fluorescence/MRI Dual-Modal Probe

Abstract

A new Gadolinium(III)–coumarin complex, DO3A-Gd-CA, was designed and prepared as a dual-modal probe for simultaneous fluorescence and relaxivity responses to fluoride ions (F−) in aqueous media and mice. DO3A-Gd-CA was designed by using Gd(III) center as an MRI signal output unit and fluoride binding site, and the 4-(diethylamino)-coumarin-3-carboxylic acid (CA) as a fluorescence reporter. Upon the addition of fluoride ions to the solution of DO3A-Gd-CA, the liberation of the coordinated CA ligand led to a 5.7-fold fluorescence enhancement and a 75% increase in the longitudinal relaxivity (r1). The fluorescent detection limit for fluoride ions was determined to be 8 μM based on a 3σ/slope. The desirable features of the proposed DO3A-Gd-CA, such as high sensitivity and specificity, reliability at physiological pH and low cytotoxicity enable its application in visualization of fluoride ion in mice. The successful in vivo imaging indicates that DO3A-Gd-CA could be potentially used in biomedical diagnosis fields.

Fluorescent “Turn-Off” Detection of Fluoride and Cyanide Ions Using Zwitterionic Spirocyclic Meisenheimer Compounds

“…In this sense, there are several promising anion chemosensors based on colorimetric changes or change in fluorescence. These gadolinium (III) organometallic complex-based sensors found promising use for in vivo imaging and fluorescence detection of biologically harmful fluoride ions [ 12 , 13 , 14 ]. Note that excess fluoride ions in biological fluids and tissues can lead to fluorosis and osteoscaroma, whereas a fluoride deficiency causes osteoporosis and poor dental health [ 15 ].…”

Recent developments in multimodality fluorescence imaging probes

“…However, the probe accumulation in the tumors were only detected by OFI, but not MRI, suggesting the necessity for further improvement of the local concentration of MRI contrast agents. Gadolinium(III)-fluorescent dye complexes can also function as activatable MRI and OFI probes for ion detection through ion exchange reaction 58 , 59 , 60 . During the process, the fluorescent dye changes from coordination with Gd(III) to free state or complexation with another metal cation, and generates fluorescence change.…”

“…The signal changes in OFI and MRI modalities and therefore gives more reliable detection of the ion of interest. Recently, Wang et al 59 reported a coumarin dye-Gd(III)-DO3A complex as a dual-modality OFI/MRI probe for fluoride anion detection. The replacement of the coumarin dye by F − increased the r 1 value from 1.67 to 2.957 (mmol/L) −1 s −1 and resulted in bright spots in T 1 -weighted MRI images in a concentration-dependent manner; a ratiometric response of fluorescence emission from 470 to 460 nm was simultaneously observed.…”

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Figure 5 An example of activatable dual-modality OFI/MRI imaging probe for detection of fluorine ion based on Gd(III) complex (Adapted with permission from the Ref. 59 . Copyright©2016 by the reference's authors; licensee MDPI, Basel, Switzerland).

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

“…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).…”