Closing in on the AMPA receptor: synthesis and evaluation of 2-acetyl-1-(4'-chlorophenyl)-6-methoxy-7-[11C]methoxy-1,2,3,4-tetrahydroisoquinoline as a potential PET tracer

Bioorganic & Medicinal Chemistry
Erik ArstadSajinder K Luthra

Abstract

2-Acetyl-1-(4'-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline, one of the most potent non-competitive AMPA antagonists described to date, has been labelled with carbon-11 and tritium and evaluated as a potential ligand for in vivo imaging of AMPA receptors using PET. The carbon-11 labelled compound showed good initial brain uptake in rats, but with rapid clearance and relatively homogenous distribution. In saturation binding studies, the tritiated racemic ligand was found to be highly potent with a Kd of 14.8+/-1.8 nM. We conclude that the low receptor density labelled with this compound, its rapid clearance from the CNS and low specific binding makes it unsuitable as an in vivo PET imaging agent for AMPA receptors.

Citations

Nov 4, 2016·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Gang ChengAbass Alavi
Sep 3, 2008·Bioorganic & Medicinal Chemistry·Rosanna StancanelliValentina Venuti
Jan 22, 2020·Nature Medicine·Tomoyuki MiyazakiTakuya Takahashi
Jan 13, 2021·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Tomoyuki MiyazakiTakuya Takahashi

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