In vivo kinetics of [18F](N-methyl)benperidol: a novel PET tracer for assessment of dopaminergic D2-like receptor binding.
A novel D2-like receptor-binding radioligand, [18F](N-methyl)benperidol ([18F]NMB), was evaluated via positron emission tomographic (PET) imaging studies of baboons. [18F]NMB rapidly localized in vivo within dopaminergic receptor-rich cerebral tissues, and striatum-to-cerebellum ratios as high as 35 were achieved after 3 hours. Pretreatment of an animal with unlabeled receptor-specific antagonists before injection of [18F]NMB confirmed that the radioligand bound specifically to central D2-like receptors in vivo, and not to S2- or D1-like receptors. Unlabeled eticlopride displaced striatal [18F]NMB in vivo, showing that D2-like binding is reversible. Receptor-binding by the radioligand was resistant to competitive displacement by synaptic dopamine, as illustrated by the lack of effect of intravenous d-amphetamine on the in vivo localization of [18F]NMB. Studies involving sequential intravenous administration of [18F]NMB, d-amphetamine, and eticlopride show that the radioligand does not undergo agonist-mediated internalization with subsequent trapping. The feasibility of applying a three-compartment non-steady state model for quantification of [18F]NMB receptor binding was demonstrated. These in vivo characteristics give [18F]NMB distinct advantages over the PET radiopharmaceuticals currently used for clinical investigation of D2-like receptor binding.
Moerlein
S M
SM
Edward Mallinckrodt Institute of Radiology, St Louis, MO 63110, USA.
Perlmutter
J S
JS
Markham
J
J
Welch
M J
MJ
D000818:Animals; D001544:Benperidol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D001921:Brain / Q000378:metabolism*; D010215:Papio; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D014055:Tomography, Emission-Computed
D017448:Receptors, Dopamine D2; C066786:N-methylbenperidol; D001544:Benperidol