Enzymatic fluorination of biotin and tetrazine conjugates for pretargeting approaches to positron emission tomography imaging
journal contributionposted on 14.01.2019, 16:35 by Phillip T. Lowe, Sergio Dall'Angelo, Andrew Devine, Matteo Zanda, David O'Hagan
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.