title: Dopamine D3 receptor antagonists: the quest for a potentially selective PET ligand. Part 3: Radiosynthesis and in vivo studies.
abstract: Compound 1 is a potent and selective antagonist of the dopamine D(3) receptor. With the aim of developing a carbon-11 labeled ligand for the dopamine D(3) receptor, 1 was selected as a potential PET probe. [(11)C]1 was obtained by palladium catalyzed cross coupling using [(11)C]cyanide and 4 with a specific activity of 55.5+/-25.9GBq/micromol (1.5+/-0.7Ci/micromol). [(11)C]1 was tested in porcine and non-human primate models to assess its potential as a radioligand for PET imaging of the dopamine D(3) receptor. We conclude that in both species and despite appropriate in vitro properties, [(11)C]1 does not show any specific signal for the dopamine D(3) receptor.
authors.affiliation: GlaxoSmithKline Clinical Imaging Centre, Imperial College London, Hammersmith Hospital, Du Cane Road, London, UK.
authors.forename: Idriss
authors.initials: I
authors.lastname: Bennacef
authors.forename: Cristian A
authors.initials: CA
authors.lastname: Salinas
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Bonasera
authors.forename: Roger N
authors.initials: RN
authors.lastname: Gunn
authors.forename: Hélène
authors.initials: H
authors.lastname: Audrain
authors.forename: Steen
authors.initials: S
authors.lastname: Jakobsen
authors.forename: Nabeel
authors.initials: N
authors.lastname: Nabulsi
authors.forename: David
authors.initials: D
authors.lastname: Weinzimmer
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Huang
authors.forename: Ian
authors.initials: I
authors.lastname: Holmes
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Micheli
authors.forename: Christian
authors.initials: C
authors.lastname: Heidbreder
authors.forename: Gabriella
authors.initials: G
authors.lastname: Gentile
authors.forename: Tino
authors.initials: T
authors.lastname: Rossi
authors.forename: Marc
authors.initials: M
authors.lastname: Laruelle
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes / Q000737:chemistry; D000882:Haplorhini; D006801:Humans; D048289:Imidazolidines / Q000138:chemical synthesis* / Q000737:chemistry; D008024:Ligands; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry; D051381:Rats; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013552:Swine
chemical_list: D002250:Carbon Radioisotopes; D048289:Imidazolidines; D008024:Ligands; D010880:Piperidines; D019275:Radiopharmaceuticals; D050637:Receptors, Dopamine D3