Abstract
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.
Original language | English |
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Pages (from-to) | 1969-1978 |
Number of pages | 10 |
Journal | ChemBioChem |
Volume | 19 |
Issue number | 18 |
Early online date | 8 Aug 2018 |
DOIs | |
Publication status | Published - 17 Sept 2018 |
Bibliographical note
Engineering and Physical Sciences Research Council. Grant Number: EP/M01262X/1Keywords
- flourinase
- amide bioconjugation
- tetrazine
- biotin
- 18F labelling