18F-Radiochemistry for Positron Emission Tomography

The Gouverneur laboratory has invented methods for the incorporation of the cyclotron-produced radioisotope F-18 into small molecules and peptides for applications in Positron Emission Tomography Imaging. Highlights include (i) novel ¹⁸F-labelled reagents for (asymmetric) ¹⁸F-fluorination (ACIE 2011), ¹⁸F-difluoromethylation (ACIE 2015) and ¹⁸F-trifluoromethylation (Nat. Chem. 2013, JACS 2018, JACS 2020), (ii) a Cu-mediated ¹⁸F-fluorination of arylboron reagents with readily available [¹⁸F]fluoride, a method used by radiochemists in PET centres worldwide (ACIE 2014, JACS 2017), (iii) difluorocarbene chemistry for accessing [¹⁸F]trifluoro(hetero)arenes from aryl iodides and [¹⁸F]fluoride (Nat Chem 2013), (iv) a pyridinium-mediated ¹⁸F-fluorination S_NAr method of (hetero)anilines (ACIE 2024), (v) a photoredox nucleophilic (radio)fluorination using TEMPO-derived alkoxyamines (JACS 2024), and (iv) the radiosynthesis of [¹⁸F]difluorocarbene and its application to insertions, cycloadditions and cross-coupling reactions (Nature 2022). These ¹⁸F-fluorination methods enabled the automated production of [¹⁸F]Olaparib, [¹⁸F]Rucaparib  and [¹⁸F]Flumazenil  currently undergoing (pre)clinical studies. With Prof. B. Davis and Prof. D. Anthony, she launched the new initiative OXIME (Oxford Molecular Imaging Epicentre). This research hub, equipped with state-of-the-art equipment, aims at inventing the next generation of PET radiotracers to investigate cancer biology, brain and heart function, and to support diagnostic and drug discovery campaigns.