A better way to add radioactive fluorine

Making compounds that contain the useful radioisotope fluorine-18 (¹⁸F) could be much easier in future, say researchers in the UK and Finland. The team integrated the isotope into a popular fluorinating agent called Selectfluor, which opens up a wide range of chemistry to build useful radiolabelled molecules. 

¹⁸F has a half-life of around 2 hours and releases positrons as it decays, making it perfect as a radiotracer in positron emission tomography (PET). This type of medical imaging is increasingly popular for disease diagnosis and monitoring a patient’s response to therapy, but it also has great potential in drug discovery.

By adding ¹⁸F to the organic structure of new drug candidates, PET scanning can be used to identify the biological interactions of the compounds. This gives chemists valuable information about the behaviour of new drugs early in their development, which helps pharmaceutical companies to make important decisions sooner in the pipeline. 

But making compounds that contain ¹⁸F is awkward, explains V?ronique Gouverneur, who led the research at the University of Oxford, UK. ’The only way to carry out electrophilic fluorination has been to use fluorine gas (F₂), which is extremely reactive and corrosive. Very few places have the facilities to manipulate this dangerous gas.’ 

The high reactivity is a problem because F₂ gas often over-fluorinates complex molecules or causes unintended side-reactions. Also, F₂ gas containing two atoms of ¹⁸F is hard to make - so the large amount of normal ¹⁹F present means the amount of radioactive fluorine incorporated in the target molecule can be quite low.  

To solve these problems, Gouverneur’s team built ¹⁸F into a popular fluorinating agent called Selectfluor. The reagent is nontoxic and undergoes a variety of fluorination reactions that are quick and easy to handle. ’Our reagent has a much better reactivity and selectivity profile, and can be easily transported short distances to local sites that do not have the capacity to manufacture it themselves,’ Gouverneur told Chemistry World. 

’Selectfluor has been around for almost two decades now, and is the most versatile electrophilic fluorinating agent out there,’ says Tobias Ritter, a fluorine chemist at Harvard University in Cambridge, US. ’Access to this labelled chemical will allow chemists to tap into a large manifold of reactions that could be extremely useful in the pharmaceutical industry.’ 

Lewis Brindley