title: 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.
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.
authors.affiliation: Hammersmith Imanet Ltd, Cyclotron Building, Du Cane Road, W12 ONN, London, UK. erik.arstad@csc.mrc.ac.uk
authors.forename: Erik
authors.initials: E
authors.lastname: Arstad
authors.forename: Rosaria
authors.initials: R
authors.lastname: Gitto
authors.forename: Alba
authors.initials: A
authors.lastname: Chimirri
authors.forename: Roberta
authors.initials: R
authors.lastname: Caruso
authors.forename: Andrew
authors.initials: A
authors.lastname: Constanti
authors.forename: David
authors.initials: D
authors.lastname: Turton
authors.forename: Sue P
authors.initials: SP
authors.lastname: Hume
authors.forename: Rabia
authors.initials: R
authors.lastname: Ahmad
authors.forename: Lyn S
authors.initials: LS
authors.lastname: Pilowsky
authors.forename: Sajinder K
authors.initials: SK
authors.lastname: Luthra
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002250:Carbon Radioisotopes; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D049268:Positron-Emission Tomography; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors* / Q000378:metabolism; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
chemical_list: C470657:2-acetyl-1-(4'-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline; D002250:Carbon Radioisotopes; D008024:Ligands; D018091:Receptors, AMPA; D044005:Tetrahydroisoquinolines