%0 Journal Article %A Lowe, Phillip T. %A Dall'Angelo, Sergio %A Devine, Andrew %A Zanda, Matteo %A O'Hagan, David %D 2019 %T Enzymatic fluorination of biotin and tetrazine conjugates for pretargeting approaches to positron emission tomography imaging %U https://repository.lboro.ac.uk/articles/journal_contribution/Enzymatic_fluorination_of_biotin_and_tetrazine_conjugates_for_pretargeting_approaches_to_positron_emission_tomography_imaging/9390782 %2 https://repository.lboro.ac.uk/ndownloader/files/17004218 %K 18F labeling %K Biotin %K Fluorinase %K Imaging agents %K Radiopharmaceuticals %K Chemical Sciences not elsewhere classified %X The use of radiolabelled antibodies and antibody-derived recombinant constructs has shown promise for both imaging and therapeutic use. In this context, the biotin–avidin/streptavidin pairing, along with the inverse-electron-demand Diels–Alder (iEDDA) reaction, have found application in pretargeting approaches for positron emission tomography (PET). This study reports the fluorinase-mediated transhalogenation [5′-chloro-5′-deoxyadenosine (ClDA) substrates to 5′-fluoro-5′-deoxyadenosine (FDA) products] of two antibody pretargeting tools, a FDA-PEG-tetrazine and a [18F]FDA-PEG-biotin, and each is assessed either for its compatibility towards iEDDA ligation to trans-cyclooctene or for its affinity to avidin. A protocol to avoid radiolytically promoted oxidation of biotin during the synthesis of [18F]FDA-PEG-biotin was developed. The study adds to the repertoire of conjugates for use in fluorinase-catalysed radiosynthesis for PET and shows that the fluorinase will accept a wide range of ClDA substrates tethered at C-2 of the adenine ring with a PEGylated cargo. The method is exceptional because the nucleophilic reaction with [18F]fluoride takes place in water at neutral pH and at ambient temperature. %I Loughborough University