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Enzymatic fluorination of biotin and tetrazine conjugates for pretargeting approaches to positron emission tomography imaging

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posted on 14.01.2019 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.

Funding

We thank the Engineering and Physical Sciences Research Council, UK, for a research grant.

History

School

  • Science

Department

  • Chemistry

Published in

ChemBioChem

Volume

19

Issue

18

Pages

1969 - 1978

Citation

LOWE, P.T. ... et al, 2018. Enzymatic fluorination of biotin and tetrazine conjugates for pretargeting approaches to positron emission tomography imaging. ChemBioChem, 19 (18), pp.1969-1978.

Publisher

© Wiley

Version

AM (Accepted Manuscript)

Publisher statement

This work is made available according to the conditions of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) licence. Full details of this licence are available at: https://creativecommons.org/licenses/by-nc-nd/4.0/

Publication date

2018-07-02

Notes

This is the peer reviewed version of the following article: LOWE, P.T. ... et al, 2018. Enzymatic fluorination of biotin and tetrazine conjugates for pretargeting approaches to positron emission tomography imaging. ChemBioChem, 19 (18), pp.1969-1978, which has been published in final form at https://doi.org/10.1002/cbic.201800234. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.

ISSN

1439-4227

eISSN

1439-7633

Language

en

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