title: A PET-study of [11C]FLB 457 binding to extrastriatal D2-dopamine receptors in healthy subjects and antipsychotic drug-treated patients.
abstract: We recently developed [11C]FLB 457 a substituted benzamide with the very high affinity of 20 pM for D2-dopamine receptors in vitro. The aim of the present exploratory study was to examine the anatomical distribution of [11C]FLB 457 binding in the human brain and to determine extrastriatal D2-receptor occupancy in antipsychotic drug-treated patients. [11C]raclopride was used to obtain reference values for D2-dopamine receptor occupancy in the putamen. After IV injection of [11C]FLB 457 there was a high concentration of radioactivity, not only in the caudate putamen but also in the thalamus and the temporal cortex. The concentration of radioactivity in the frontal cortex, the substantia nigra and the colliculi was slightly higher than in the cerebellum. Pretreatment with haloperidol and fluphenazine indicated that [11C]FLB 457 binding in extrastriatal regions to a high degree represent specific binding to D2-dopamine receptors. The D2-occupancy in antipsychotic drug-treated patients was on the same level in the thalamus and the temporal cortex as that determined with [11C]raclopride in the putamen. The study shows that [11C]FLB 457 has potential for quantitative PET-examination of D2-dopamine receptors in man.
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. larsf@psyk.ks.se
authors.forename: L
authors.initials: L
authors.lastname: Farde
authors.forename: T
authors.initials: T
authors.lastname: Suhara
authors.forename: S
authors.initials: S
authors.lastname: Nyberg
authors.forename: P
authors.initials: P
authors.lastname: Karlsson
authors.forename: Y
authors.initials: Y
authors.lastname: Nakashima
authors.forename: J
authors.initials: J
authors.lastname: Hietala
authors.forename: C
authors.initials: C
authors.lastname: Halldin
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000000981:diagnostic imaging; D001923:Brain Chemistry / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000493:pharmacokinetics*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D011759:Pyrrolidines / Q000493:pharmacokinetics*; D020891:Raclopride; D011869:Radioligand Assay; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D012457:Salicylamides / Q000493:pharmacokinetics*; D014055:Tomography, Emission-Computed
chemical_list: D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D012457:Salicylamides; C065065:FLB 457; D020891:Raclopride