Specific binding of 3N-(2'-[18F]fluoroethyl)benperidol to primate cerebral dopaminergic D2 receptors demonstrated in vivo by PET.
3N-(2'-[18F]Fluoroethyl)benperidol ([18F]FEB) an 18F-labeled analogue of the D2 antagonist benperidol, was evaluated as a tracer for positron emission tomography (PET). PET imaging of a living baboon showed that the fluorinated ligand rapidly localized in vivo within D2 receptor-rich brain tissue, with selective retention lasting over 2 h after tracer injection. Pretreatment of the animal with unlabeled D2-specific antagonist eticlopride (4 mg/kg, i.v.) 1 h before [18F]FEB completely abolished the selective disposition of the radioligand, whereas the regional cerebral blood flow, blood volume and peripheral metabolism/protein binding of [18F]FEB were not changed. Tracer localization when the baboon was pretreated with unlabeled ketanserin (0.55 mg/kg, i.v.) or SCH 23390 (1.1 mg/kg, i.v.) was identical to that for the control case, indicating that the [18F]FEB did not bind to S2 of D1 receptors in vivo. [18F]FEB has advantages compared to previously used PET tracers, and may be an excellent radioligand for non-invasive study of D2 receptor binding.
Moerlein
S M
SM
Edward Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110.
Perlmutter
J S
JS
D000818:Animals; D001479:Basal Ganglia / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D001544:Benperidol / Q000031:analogs & derivatives* / Q000378:metabolism; D001552:Benzazepines / Q000494:pharmacology; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000378:metabolism; D065127:Dopamine D2 Receptor Antagonists; D005462:Fluorine Radioisotopes; D007650:Ketanserin / Q000494:pharmacology; D007700:Kinetics; D010215:Papio; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D012457:Salicylamides / Q000494:pharmacology; D014055:Tomography, Emission-Computed / Q000379:methods
D001552:Benzazepines; D065127:Dopamine D2 Receptor Antagonists; D005462:Fluorine Radioisotopes; D017448:Receptors, Dopamine D2; D012457:Salicylamides; C080887:3N-(2'-fluoroethyl)benperidol; D007650:Ketanserin; D001544:Benperidol; C045989:eticlopride