title: Autoradiography of 2-[18F]F-A-85380 on nicotinic acetylcholine receptors in the porcine brain in vitro.
abstract: Noninvasive molecular imaging of subtypes of neuronal nicotinic acetylcholine receptors (nAChRs) will provide information on the role of these receptors in neurodegenerative diseases. The binding of the positron emission tomography ligand 2-[18F]F-A-85380 to nAChRs was investigated in the porcine brain by quantitative autoradiography in vitro. The high-affinity binding of 2-[18F]F-A-85380 to each of the investigated 12 brain areas was saturable and apparently monophasic (e.g., apparent KD value of 1.72 nM in the thalamus). The highest density of specific binding sites was observed in the thalamus (1,158 fmol/mg protein), and the lowest density was measured in the cerebellar gray matter (11 fmol/mg protein). An attempt to assess nAChR subtype specificity of 2-[18F]F-A-85380 was made by competitive autoradiography. Binding of 2-[18F]F-A-85380 coincubated with 2-F-A-85380, epibatidine, cytisine, or methyllycaconitine, respectively, indicated a specificity of 2-[18F]F-A-85380 to beta2-containing nAChRs in the porcine brain. The autoradiographic data confirmed the suitability of swine as a model for the evaluation of radioligands designed for imaging of nAChR subtypes in the living brain.
authors.affiliation: Institute of Interdisciplinary Isotope Research, Radiopharmacy, 04318 Leipzig, Germany. conrad@iif-leipzig.de
authors.forename: Winnie
authors.initials: W
authors.lastname: Deuther-Conrad
authors.forename: Andrea
authors.initials: A
authors.lastname: Wevers
authors.forename: Georg
authors.initials: G
authors.lastname: Becker
authors.forename: Andreas
authors.initials: A
authors.lastname: Schildan
authors.forename: Marianne
authors.initials: M
authors.lastname: Patt
authors.forename: Osama
authors.initials: O
authors.lastname: Sabri
authors.forename: Jörg
authors.initials: J
authors.lastname: Steinbach
authors.forename: Peter
authors.initials: P
authors.lastname: Brust
mesh_terms: D000818:Animals; D001345:Autoradiography; D001384:Azetidines / Q000378:metabolism / Q000493:pharmacokinetics*; D001667:Binding, Competitive; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009924:Organ Culture Techniques; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000378:metabolism / Q000493:pharmacokinetics*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013552:Swine
chemical_list: C119803:2-fluoro-3-(2-azetidinylmethoxy)pyridine; D001384:Azetidines; D011725:Pyridines; D011978:Receptors, Nicotinic