The use of radiolabelled antibodies and antibody-derived recombinant constructs have shown promise for both imaging and therapeutic use. In this context, the biotin-avidin/streptavidin pairing along with the inverse electron demand Diels–Alder reaction (IEDDA) have found application in pre-targeting approaches for positron emission tomography (PET). This study reports the fluorinase enzyme mediated transhalogenation (ClDA substrates to FDA products) of two antibody pre-targeting tools, a FDA-PEG-tetrazine and a [18F]FDA-PEG-biotin and each is assessed for their compatibility towards IEDDA ligation to trans-cyclooctene or affinity to avidin. A protocol was developed to avoid radiolytically promoted oxidation of biotin during the synthesis of [18F]FDA-PEG-biotin. The study adds to the repertoire of conjugates for use in fluorinase catalysed radio-synthesis 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 as the nucleophilic reaction with [18F]fluoride takes place in water at neutral pH and at ambient temperature.
- amide bioconjugation
- 18F labelling
Lowe, P. T., Dall'angelo, S., Devine, A., Zanda, M., & O'Hagan, D. (2018). Enzymatic Fluorination of Biotin and Tetrazine Conjugates for Pretargeting Approaches to Positron Emission Tomography Imaging. ChemBioChem, 19(18), 1969-1978. https://doi.org/10.1002/cbic.201800234