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Fully Automated Synthesis and Evaluation of [ 18 F]BPAM121: Potential of an AMPA Receptor Positive Allosteric Modulator as PET Radiotracer
Author(s) -
ManosTurvey Alexandra,
Becker Guillaume,
Francotte Pierre,
Serrano Maria Elisa,
Luxen André,
Pirotte Bernard,
Plenevaux Alain,
Lemaire Christian
Publication year - 2019
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201800816
Subject(s) - ampa receptor , allosteric regulation , allosteric modulator , positron emission tomography , in vivo , pharmacology , radiosynthesis , chemistry , receptor , neuroscience , glutamate receptor , biochemistry , medicine , psychology , biology , genetics
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.