title: Imaging of central nAChReceptors with 2-[18F]F-A85380: optimized synthesis and in vitro evaluation in Alzheimer's disease.
abstract: In vivo labeling of the nicotinic acetylcholine receptors (nAChR) could be a useful tool for early diagnosis of neurodegenerative disorders. 2-[18F]F-A85380 (2-[18F]Fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine), a ligand with high affinity to the beta2 subunit of the nAChRs, has been shown to label neurons in the nAChR-rich thalamus, cortex and striatum in baboons. We report an optimized synthesis resulting in an uncorrected yield of 58% in 45 min (precursor 2), enabling efficient production intended for clinical use. Incubation of normal rat brain sections with 2-[18F]F-A85380 with subsequent autoradiographic analyses showed the expected distribution in nAChR areas. In human brain sections of Alzheimer's disease (AD) a decrease of 2-[18F]F-A85380 uptake to 36% of the control group was measured in the thalamus and also in the occipital cortex. These findings suggest that 2-[18F]F-A85380 is a promising PET-ligand in the diagnosis of AD.
authors.affiliation: Department of Neurology, University of Bonn, 53105 Bonn, Germany. joern.schmaljohann@ukb.uni-bonn.de
authors.forename: J
authors.initials: J
authors.lastname: Schmaljohann
authors.forename: M
authors.initials: M
authors.lastname: Minnerop
authors.forename: P
authors.initials: P
authors.lastname: Karwath
authors.forename: D
authors.initials: D
authors.lastname: Gündisch
authors.forename: P
authors.initials: P
authors.lastname: Falkai
authors.forename: S
authors.initials: S
authors.lastname: Guhlke
authors.forename: U
authors.initials: U
authors.lastname: Wüllner
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism*; D000818:Animals; D001384:Azetidines / Q000737:chemistry / Q000493:pharmacokinetics*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005462:Fluorine Radioisotopes / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: C104288:A 85380; D001384:Azetidines; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D011978:Receptors, Nicotinic