18F-radiopharmaceutical diversification enabled by deaminative cross-electrophile couplings

Ogilvy, Isabella F., Ford, Joseph, Ortalli, Sebastiano, Renders, Evelien, Hayes, Thomas R., Liu, Shuanglong, Mortiers, Inne, Nikolopoulou, Anastasia, Sorlin, Alexandre M., Trabanco, Andrés A., Tredwell, Matthew ORCID: https://orcid.org/0000-0002-4184-5611, Buijnsters, Peter J. J. A., Salter, Rhys and Gouverneur, Véronique 2025. 18F-radiopharmaceutical diversification enabled by deaminative cross-electrophile couplings. Angewandte Chemie International Edition , e22650. 10.1002/anie.202522650

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Abstract

The development of 18F-labelled radiotracers is of vital importance for (pre)clinical positron emission tomography (PET) imaging and to guide drug discovery campaigns. State-of-the-art approaches often require labour-intensive preparation of highly functionalised radiolabelling precursors. This bottleneck impedes analogue generation for optimal imaging and exploration of radiochemical space. To this end, we disclose a nickel-mediated aryl (C)sp2-(C)sp3 cross-coupling with amine-derived alkyl 2,4,6-triphenylpyridinium salts as coupling partners amenable to radiosynthesis. The method was applied to primary and secondary 2,4,6-triphenylpyridinium salts in radiochemical conversion (RCC) up to 86% and a high-throughput experimentation (HTE) assay proved crucial for expedient ligand evaluation. A late-stage diversification case study from a sole precursor achieved six 18F-labelled GSK-3 kinase inhibitor analogues, one being prepared in up to gigabecquerel (GBq) quantities in a (semi)automated two-step protocol applied across three commercial radiosynthesis platforms.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Schools > Chemistry Research Institutes & Centres > Wales Research Diagnostic Pet Imaging Centre (PETIC)
Publisher:	Wiley
ISSN:	1433-7851
Date of First Compliant Deposit:	9 December 2025
Date of Acceptance:	25 November 2025
Last Modified:	09 Dec 2025 09:30
URI:	https://orca.cardiff.ac.uk/id/eprint/183000

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