King's College London

Research portal

Fully Automated Synthesis and Evaluation of [18 F]BPAM121: Potential of an AMPA Receptor Positive Allosteric Modulator as PET Radiotracer

Research output: Contribution to journalArticle

Alexandra Manos-Turvey, Guillaume Becker, Pierre Francotte, Maria Elisa Serrano, André Luxen, Bernard Pirotte, Alain Plenevaux, Christian Lemaire

Original languageEnglish
Pages (from-to)788-795
Number of pages8
JournalChemmedchem
Volume14
Issue number7
DOIs
Published3 Apr 2019

Bibliographical note

© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

King's Authors

Abstract

Alzheimer's disease (AD) remains a significant burden on society. In the search for new AD drugs, modulators of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are of particular interest, as loss of synaptic AMPARs has been linked to AD learning and memory deficits. Previously reported fluorine-containing BPAM121, an AMPA positive allosteric modulator (pam) with high activity, low toxicity, and slow metabolism, was considered to be a perfect 18 F-labeled candidate for positron emission tomography (PET) AD diagnostic investigations. For the preclinical use of this compound, an automated synthesis avoiding human radiation exposure was developed. The detailed production of [18 F]BPAM121 in relatively high quantity using a commercial FASTlab synthesizer from GE Healthcare coupled with a full set of quality controls is presented, along with procedures for the synthesis of the tosylated precursor and the fluorinated reference. To evaluate the clinical usefulness of [18 F]BPAM121 as a potential AD diagnostic, some in vivo studies in mice were then realized, alongside blocking and competition studies.

View graph of relations

© 2020 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454