title: 5-(5-(6-[(11)C]methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)pyridin-2-yl)-1H-indole as a potential PET radioligand for imaging cerebral α7-nAChR in mice.
abstract: The radiosynthesis and in vivo evaluation of 5-(5-(6-[(11)C]methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)pyridin-2-yl)-1H-indole [(11)C]rac-(1), a potential PET tracer for α7 nicotinic acetylcholine receptors (α7-nAChR), are described. Syntheses of the nonradioactive standard rac-1 and corresponding desmethyl precursor 7 were achieved in several reaction steps. Radiomethylation of 7 with [(11)C]CH(3)I afforded [(11)C]rac-1 in an average radiochemical yield of 30 ± 5% (n=5) with high radiochemical purity and an average specific radioactivity of 444 ± 74 GBq/μmol (n=5). The total synthesis time was 30 min from end-of-bombardment. Biodistribution studies in mice showed that [(11)C]rac-1 penetrates the blood-brain barrier and specifically labels neuronal α7-nAChRs.
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, The Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287-0816, USA. ygao5@jhmi.edu
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Gao
authors.forename: Hayden T
authors.initials: HT
authors.lastname: Ravert
authors.forename: Heather
authors.initials: H
authors.lastname: Valentine
authors.forename: Ursula
authors.initials: U
authors.lastname: Scheffel
authors.forename: Paige
authors.initials: P
authors.lastname: Finley
authors.forename: Dean F
authors.initials: DF
authors.lastname: Wong
authors.forename: Robert F
authors.initials: RF
authors.lastname: Dannals
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Horti
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D007211:Indoles / Q000037:antagonists & inhibitors; D008024:Ligands; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000037:antagonists & inhibitors; D011812:Quinuclidines / Q000494:pharmacology; D019275:Radiopharmaceuticals / Q000037:antagonists & inhibitors / Q000737:chemistry; D011978:Receptors, Nicotinic / Q000032:analysis* / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C576514:5-(5-(6-((11)C)methyl-3,6-diazabicyclo(3.2.0)heptan-3-yl)pyridin-2-yl)-1H-indol; D019086:Bridged Bicyclo Compounds, Heterocyclic; C579166:Chrna7 protein, mouse; D007211:Indoles; D008024:Ligands; C513163:N-(1-azabicyclo(2.2.2)oct-3-yl)furo(2,3-c)pyridine-5-carboxamide; D011725:Pyridines; D011812:Quinuclidines; D019275:Radiopharmaceuticals; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor