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)

Research output: Contribution to journalArticle

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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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Fluorination
Positron emission tomography
Halogenation
Biotin
Positron-Emission Tomography
Polyethylene glycols
Imaging techniques
Avidin
Antibodies
Electrons
Streptavidin
Therapeutic Uses
Adenine
Substrates
Radio
Fluorides
Ligation
Oxidation
Temperature
Water

Keywords

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

Cite this

Enzymatic Fluorination of Biotin and Tetrazine Conjugates for Pretargeting Approaches to Positron Emission Tomography Imaging. / Lowe, Philip T.; Dall'angelo, Sergio; Devine, Andrew; Zanda, Matteo (Corresponding Author); O'Hagan, David (Corresponding Author).

In: ChemBioChem, Vol. 19, No. 18, 17.09.2018, p. 1969-1978.

Research output: Contribution to journalArticle

Lowe, Philip T. ; Dall'angelo, Sergio ; Devine, Andrew ; Zanda, Matteo ; O'Hagan, David. / Enzymatic Fluorination of Biotin and Tetrazine Conjugates for Pretargeting Approaches to Positron Emission Tomography Imaging. In: ChemBioChem. 2018 ; Vol. 19, No. 18. pp. 1969-1978.
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