title: 6-[18F]fluoro-A-85380, a novel radioligand for in vivo imaging of central nicotinic acetylcholine receptors.
abstract: A novel positron emission tomography (PET) radiotracer, 6-[18F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (6-[18F]fluoro-A-85380, 6-[18F]FA) was synthesized by a no-carrier-added fluorination. In vitro 6-[18F]FA bound to nicotinic acetylcholine receptors (nAChRs), with very high affinity (Kd 28 pM). In PET studies, 6-[18F]FA specifically labeled central nAChRs in the brain of the Rhesus monkey and demonstrated highest levels of accumulation of radioactivity in brain regions enriched with the alpha4beta2 subtype of nAChR. 6-[18F]FA exhibited a target-to-non-target ratio (estimated as radioactivity in the thalamus to that in the cerebellum) of binding in primate brain similar to that previously determined for a labeled analog of epibatidine, [18F]FPH. In contrast to [18F]FPH, the novel tracer is expected to exhibit substantially less toxicity. Thus, the novel radioligand, 6-[18F]FA, appears to be a suitable candidate for imaging nAChRs in human brain.
authors.affiliation: Brain Imaging Center, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: A G
authors.initials: AG
authors.lastname: Horti
authors.forename: S I
authors.initials: SI
authors.lastname: Chefer
authors.forename: A G
authors.initials: AG
authors.lastname: Mukhin
authors.forename: A O
authors.initials: AO
authors.lastname: Koren
authors.forename: D
authors.initials: D
authors.lastname: Gündisch
authors.forename: J M
authors.initials: JM
authors.lastname: Links
authors.forename: V
authors.initials: V
authors.lastname: Kurian
authors.forename: R F
authors.initials: RF
authors.lastname: Dannals
authors.forename: E D
authors.initials: ED
authors.lastname: London
mesh_terms: D000818:Animals; D001384:Azetidines / Q000138:chemical synthesis; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005462:Fluorine Radioisotopes; D008253:Macaca mulatta; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011978:Receptors, Nicotinic / Q000032:analysis*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
chemical_list: C104288:A 85380; D001384:Azetidines; D005462:Fluorine Radioisotopes; D011978:Receptors, Nicotinic