Specific, reversible binding of [18F]benperidol to baboon D2 receptors: PET evaluation of an improved 18F-labeled ligand.
[18F]Benperidol ([18F]BP), a positron-emitting analogue of the dopaminergic D2 antagonist benperidol, was evaluated as a radiopharmaceutical for use with positron emission tomography (PET). PET imaging of baboons after i.v. injection of [18F]BP indicated that the radiofluorinated ligand rapidly localized in vivo within dopaminergic receptor-rich cerebral tissues, and that selective disposition was retained for over 2 h. Pretreatment of an animal with unlabeled receptor-specific antagonists prior to injection of [18F]BP confirmed that the radioligand bound specifically to central D2 receptors in vivo, and not to S2 or D1 receptors. [18F]BP bound to D2 receptors in a reversible manner; unlabeled eticlopride displaced D2 receptor-bound [18F]BP in vivo. The radioligand was metabolized in the periphery to polar metabolites which are not expected to cross the blood-brain barrier. [18F]BP has advantages over other tracers as a radiopharmaceutical for PET study of central D2 receptor activity, and can be applied for noninvasive evaluation of the interaction of unlabeled drugs with central D2 receptor sites.
Moerlein
S M
SM
Edward Mallinckrodt Institute of Radiology, St. Louis, MO 63110, USA.
Perlmutter
J S
JS
Welch
M J
MJ
D000818:Animals; D001544:Benperidol / Q000378:metabolism*; D001552:Benzazepines / Q000494:pharmacology; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D005462:Fluorine Radioisotopes; D007700:Kinetics; D010215:Papio; D011869:Radioligand Assay; D017448:Receptors, Dopamine D2 / Q000032:analysis / Q000378:metabolism*; D012457:Salicylamides / Q000494:pharmacology; D013997:Time Factors; D014055:Tomography, Emission-Computed
D001552:Benzazepines; D018492:Dopamine Antagonists; D005462:Fluorine Radioisotopes; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D001544:Benperidol; C045989:eticlopride