Fully automated synthesis and evaluation of [18F]BPAM121: Potential of an AMPA receptor positive allosteric modulator as PET radiotracer.

Fully automated synthesis and evaluation of [18F]BPAM121: Potential of an AMPA receptor positive allosteric modulator as PET radiotracer.
ChemMedChem. 2019 Feb 11;:
Authors: Manos-Turvey A, Becker G, Francotte P, Serrano ME, Luxen A, Pirotte B, Plenevaux A, Lemaire C
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 18F-labelled 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 [18F]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 starting precursor and the fluorinated reference. To evaluate the clinical usefulness of [18F]BPAM121 as a potential AD diagnostic, some in vivo studies in mice were then realized, alongside blocking and competition studies.
PMID: 30740927 [PubMed - as supplied by p...

Source: ChemMedChem - February 11, 2019 Category: Chemistry Authors: Manos-Turvey A, Becker G, Francotte P, Serrano ME, Luxen A, Pirotte B, Plenevaux A, Lemaire C Tags: ChemMedChem Source Type: research