Enzymatic Fluorination of Biotin and Tetrazine Conjugates for Pretargeting Approaches to Positron Emission Tomography Imaging

Philip T. Lowe, Sergio Dall'angelo, Andrew Devine, Matteo Zanda (Corresponding Author), David O'Hagan (Corresponding Author)

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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 languageEnglish
Pages (from-to)1969-1978
Number of pages10
JournalChemBioChem
Volume19
Issue number18
Early online date8 Aug 2018
DOIs
Publication statusPublished - 17 Sep 2018

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Keywords

  • flourinase
  • amide bioconjugation
  • tetrazine
  • biotin
  • 18F labelling

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