title: Design, synthesis and preliminary evaluation of (18)F-labelled 1,8-naphthyridin- and quinolin-2-one-3-carboxamide derivatives for PET imaging of CB2 cannabinoid receptor.
abstract: In the present work, we report the synthesis of new aryliodonium salts used as precursors of single-stage nucleophilic (18)F radiofluorination. The corresponding unlabelled fluorinated derivatives showed to be CB2 cannabinoid receptor specific ligands, with Ki values in the low nanomolar range and high CB2/CB1 selectivity. The radiolabelled compound [(18)F]CB91, was successfully formulated for in vivo administration, and its preliminary biodistribution was assessed with microPET/CT. This tracer presented a reasonable in vivo stability and a preferential extraction in the tissues that constitutionally express CB2 cannabinoid receptor. The results obtained indicate [(18)F]CB91 as a possible candidate marker of CB2 cannabinoid receptor distribution. This study would open the way to further validation of this tracer for assessing pathologies for which the expression of this receptor is modified.
authors.affiliation: Dipartimento di Farmacia, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saccomanni
authors.affiliation: CNR Istituto di Fisiologia Clinica, Via Moruzzi, 1, 56124 Pisa, Italy; ANSTO LifeSciences, PO Box M34, Camperdown 2050, Australia.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Pascali
authors.affiliation: Dipartimento di Farmacia, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
authors.forename: Sara Del
authors.initials: SD
authors.lastname: Carlo
authors.affiliation: CNR Istituto di Fisiologia Clinica, Via Moruzzi, 1, 56124 Pisa, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Panetta
authors.affiliation: CNR Istituto di Fisiologia Clinica, Via Moruzzi, 1, 56124 Pisa, Italy.
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: De Simone
authors.affiliation: Dipartimento di Farmacia, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Bertini
authors.affiliation: Fondazione Toscana G. Monasterio, Via Moruzzi, 1, 56124 Pisa, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Burchielli
authors.affiliation: Dipartimento di Farmacia, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Digiacomo
authors.affiliation: Dipartimento di Farmacia, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Macchia
authors.affiliation: Dipartimento di Farmacia, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy. Electronic address: clementina.manera@farm.unipi.it.
authors.forename: Clementina
authors.initials: C
authors.lastname: Manera
authors.affiliation: CNR Istituto di Fisiologia Clinica, Via Moruzzi, 1, 56124 Pisa, Italy.
authors.forename: Piero A
authors.initials: PA
authors.lastname: Salvadori
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D003287:Contrast Media / Q000138:chemical synthesis* / Q000737:chemistry; D015195:Drug Design; D005462:Fluorine Radioisotopes / Q000737:chemistry; D007536:Isomerism; D008297:Male; D051379:Mice; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D015363:Quinolones / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D043884:Receptor, Cannabinoid, CB1 / Q000737:chemistry / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000737:chemistry / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D000577:Amides; C000605133:CB91 compound; D003287:Contrast Media; D005462:Fluorine Radioisotopes; D009287:Naphthyridines; D015363:Quinolones; D019275:Radiopharmaceuticals; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2
keywords: CB2 receptor; Cannabinoid; Iodonium derivatives; Microfluidic system; Radiofluorination