title: [125/123I] 5-Iodo-3-pyridyl ethers. syntheses and binding to neuronal nicotinic acetylcholine receptors.
abstract: Three 3-pyridyl ether nicotinic ligands-(S)-5-Iodo-3-[(2-pyrrolidinyl)-methoxy]pyridine (5-iodo-A-85865), (S)-5-Iodo-3-[1-(methyl)-2-pyrrolidinyl-methoxy]pyridine (5-Iodo-A-84543), and (S)-5-iodo-3-[1-methyl-(2-azetidinyl)-methoxy]pyridine (5-iodo-N-Me-A-85380) were labeled with I-125/I-123, and their ability to label high-affinity brain nicotinic acetylcholine receptors (nAChRs) was evaluated. The most promising ligand, [123/125I] 5-iodo-A-85865, showed approximately 65% inhibition of radioactivity uptake in thalamus in mice pretreated with cytisine. Preliminary SPECT imaging studies with [123I] 5-iodo-A-85865 revealed a distribution profile consistent with nAChRs (thalamus > frontal cortex > cerebellum) and a more rapid pharmacokinetic profile relative to azetidinyl 3-pyridyl ether based ligands.
authors.affiliation: Johns Hopkins University School of Medicine, Department of Radiology, Division of Nuclear Medicine, Baltimore, MD 21287, USA.
authors.forename: H
authors.initials: H
authors.lastname: Fan
authors.forename: U A
authors.initials: UA
authors.lastname: Scheffel
authors.forename: P
authors.initials: P
authors.lastname: Rauseo
authors.forename: Y
authors.initials: Y
authors.lastname: Xiao
authors.forename: A S
authors.initials: AS
authors.lastname: Dogan
authors.forename: F
authors.initials: F
authors.lastname: Yokoi
authors.forename: J
authors.initials: J
authors.lastname: Hilton
authors.forename: K J
authors.initials: KJ
authors.lastname: Kellar
authors.forename: D F
authors.initials: DF
authors.lastname: Wong
authors.forename: J L
authors.initials: JL
authors.lastname: Musachio
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging*; D004987:Ethers / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D010215:Papio; D011725:Pyridines / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics; D011978:Receptors, Nicotinic / Q000378:metabolism*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D004987:Ethers; D011725:Pyridines; D011978:Receptors, Nicotinic