Enzymatic fluorination of biotin and tetrazine conjugates for pretargeting approaches to positron emission tomography imaging
journal contributionposted on 14.01.2019 by Phillip T. Lowe, Sergio Dall'Angelo, Andrew Devine, Matteo Zanda, David O'Hagan
Any type of content formally published in an academic journal, usually following a peer-review process.
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.
We thank the Engineering and Physical Sciences Research Council, UK, for a research grant.