Enzymatic Fluorination of Biotin and Tetrazine Conjugates for Pretargeting Approaches to Positron Emission Tomography Imaging |
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Authors: | Dr Phillip T Lowe Dr Sergio Dall'Angelo Andrew Devine Prof Matteo Zanda Prof David O'Hagan |
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Affiliation: | 1. School of Chemistry and Centre for Biomolecular Sciences, University of St. Andrews, St. Andrews, Fife, UK;2. John Mallard Scottish PET Centre, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK |
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Abstract: | 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. |
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Keywords: | 18F labeling biotin fluorinase imaging agents radiopharmaceuticals |
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