title: Radiosynthesis and first evaluation in mice of [(18)F]NS14490 for molecular imaging of α7 nicotinic acetylcholine receptors.
abstract: [(18)F]NS14490, a new potential radiotracer for neuroimaging of α7 nicotinic acetylcholine receptors (α7 nAChRs), was synthesized and evaluated in vitro and in vivo. Radioligand binding studies using [(3)H]methyllycaconitine and NS14490 as competitor showed a good target affinity (K(i,α7) = 2.5 nM) and a high selectivity towards other nAChRs. Radiosynthesis of [(18)F]NS14490 was performed by two different labelling procedures: a two-step synthesis using a prosthetic group, which led to 7% labelling yield, and the convenient direct nucleophilic substitution of the corresponding tosylate precursor, which resulted in 70% labelling yield. After optimisation of the isolation, purification and formulation process, biodistribution studies were performed in CD-1 mice. The brain uptake of [(18)F]NS14490 was comparably low (0.16% ID g(-1) wet weight at 5 min p.i.). The radiotracer showed a high metabolic stability in plasma and brain. Also, the target specificity was proven by pre-administration of a highly affine α7 ligand providing a rationale basis for further in vivo evaluation.
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmacy, Research Site Leipzig, Dept. of Neuroradiopharmaceuticals, Permoserstrasse 15, 04318 Leipzig, Germany. s.roetering@hzdr.de
authors.forename: Sven
authors.initials: S
authors.lastname: Rötering
authors.forename: Matthias
authors.initials: M
authors.lastname: Scheunemann
authors.forename: Steffen
authors.initials: S
authors.lastname: Fischer
authors.forename: Achim
authors.initials: A
authors.lastname: Hiller
authors.forename: Dan
authors.initials: D
authors.lastname: Peters
authors.forename: Winnie
authors.initials: W
authors.lastname: Deuther-Conrad
authors.forename: Peter
authors.initials: P
authors.lastname: Brust
mesh_terms: D000818:Animals; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D051379:Mice; D057054:Molecular Imaging; D010069:Oxadiazoles / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D011978:Receptors, Nicotinic / Q000032:analysis* / Q000378:metabolism; D014018:Tissue Distribution; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579167:Chrna7 protein, human; C579166:Chrna7 protein, mouse; D007211:Indoles; C584300:NS14490; D010069:Oxadiazoles; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor