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.
Edward Mallinckrodt Institute of Radiology, St. Louis, MO 63110, USA.
S M
SM
Moerlein
J S
JS
Perlmutter
M J
MJ
Welch
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