title: Preparation of [76Br]FLB 457 and [76Br]FLB 463 for examination of striatal and extrastriatal dopamine D-2 receptors with PET.
abstract: Both FLB 457 and FLB 463, two substituted benzamides with high affinity for the dopamine D-2 receptors, were labeled with bromine-76 for PET investigations. [76Br]FLB 457 was prepared by electrophilic substitution of the tributyltin precursor. The radiochemical yield was 80%. [76Br]FLB 463 was prepared by a direct electrophilic substitution enhanced by the hydroxyl group of the debromo analogue, with a total radiochemical yield of 50%. Radiochemical and chemical purity values of the radioligands as analyzed by radio-TLC and HPLC were > 99%, and the specific radioactivity was -40 GBq/mumol. During PET examinations of [76Br]FLB 457 and [76Br]FLB 463 binding in baboons there was a rapid and high uptake in the striatum. The striatal radioactivity concentration reached a plateau 1 h postinjection (p.i.). The striatum-to-cerebellum radioactivity concentration ratio increased from 11 at 1 h p.i., to 28 at 4 h p.i. for [76Br]FLB 457, owing to a continuous wash-out from the cerebellum. For [76Br]FLB 463 the corresponding value increased from 10 to 19.5. [76Br]FLB 457 has in contrast to [76Br]FLB 463 a high uptake in thalamic structures and has therefore an additional potential as a radioligand for PET examination of extrastriatal dopamine D-2 receptors in the living human brain.
authors.affiliation: Département de Récherche Médicale, Service Hospitalier Frédéric Joliot, Orsay, France. loch@uriens.shfj.cea.fr
authors.forename: C
authors.initials: C
authors.lastname: Loc'h
authors.forename: C
authors.initials: C
authors.lastname: Halldin
authors.forename: M
authors.initials: M
authors.lastname: Bottlaender
authors.forename: C G
authors.initials: CG
authors.lastname: Swahn
authors.forename: R M
authors.initials: RM
authors.lastname: Moresco
authors.forename: M
authors.initials: M
authors.lastname: Mazière
authors.forename: L
authors.initials: L
authors.lastname: Farde
authors.forename: B
authors.initials: B
authors.lastname: Mazière
mesh_terms: D000818:Animals; D001967:Bromine Radioisotopes; D002855:Chromatography, Thin Layer; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000648:ultrastructure*; D018492:Dopamine Antagonists / Q000138:chemical synthesis* / Q000378:metabolism*; D008297:Male; D010215:Papio; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012457:Salicylamides / Q000138:chemical synthesis* / Q000378:metabolism*; D014055:Tomography, Emission-Computed
chemical_list: D001967:Bromine Radioisotopes; D018492:Dopamine Antagonists; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D012457:Salicylamides; C065065:FLB 457; C104326:FLB 463