A ¹⁸F radiolabelled Zn(ii) sensing fluorescent probe

Abstract

A selective fluorescent probe for Zn(ii), AQA-F, has been synthesized. AQA-F exhibits a ratiometric shift in emission of up to 80 nm upon binding Zn(ii) ([AQA-F] = 0.1 mM, [Zn(ii)Cl2] = 0-300 μM). An enhancement of quantum yield from Φ = 4.2% to Φ = 35% is also observed. AQA-F has a binding constant, Kd = 15.2 μM with Zn(ii). This probe has been shown to respond to endogenous Zn(ii) levels in vitro in prostate and prostate cancer cell lines. [18F]AQA-F has been synthesized with a radiochemical yield of 8.6% and a radiochemical purity of 97% in 88 minutes. AQA-F shows the potential for a dual modal PET/fluorescence imaging probe for Zn(ii).

Recent Progress in Fluorescent Probes For Metal Ion Detection

“…Hagimori et al ( Hagimori, 2013 ) reported that novel fluorescent probes based on pyridine-pyridone possess low molecular weight for zinc ion detection. Price et al ( Price et al, 2018 ) reported AQA-F, a fluorescent probe that can be used to detect zinc ions in prostate and prostate cancer cell lines in vitro . Zhang ( Zhang et al, 2012 ) developed a pyrazoline based fluorescent probe and verified that this probe showed 40-fold enhanced fluorescence for Zn 2+ compared to other metal ions, i.e., good selectivity for Zn ions, and that it could be well applied in living neuronal cells.…”

Non-invasive radionuclide imaging of trace metal trafficking in health and disease: “PET metallomics”

“…Much effort has been invested in recent decades in the synthesis of fluorescence sensors that can be used in vitro to study zinc biology. An extensive library of such probes has been developed, [233][234][235][236][237][238][239][240][241][242] combining Zn 2+ chelating units, such as di-2picolylamine (DPA), and a fluorescent reporter that, following zinc binding, initiates a change in emission properties (e.g. quantum yield and/or wavelength).…”

“…Due to the limited tissue penetration associated with fluorescence, these probes have rarely been implemented in vivo. Recent efforts have been made to design medical imaging contrast agents to study zinc in vivo, 241,242,[245][246][247] and these have proved useful to study labile zinc pools. However, tools providing complementary information on the dynamic flux of zinc within the body are lacking.…”

“…In the context of PET imaging of metal trafficking, a 18 F radiolabelled fluorescent zinc sensor, consisting of a small lipophilic chelator that can enter cells passively and becomes trapped within them when bound to zinc ions, has recently been reported with the goal of non-invasively imaging endogenous Zn pools in vivo in diseases such as prostate cancer. 242 The biological validation and potential of such a radiolabelled probe is yet to be reported. Given the plethora of fluorescence probes for the detection of metals, other 18 F radiolabelled metal sensors can be envisaged.…”

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

“…18 F-labeled analogs of common staining dyes have also been described. Indeed, acridine orange, ethidium, anthracene, and Evans blue analogs have been radiofluorinated, but only [ 18 F]ethidium optical properties were used in a cell imaging experiment despite their red-centered emission [130][131][132][133][134].…”