Effect of Dopamine D₂ Receptor Antagonists on [¹⁸F]-FEOBV Binding

Area of Science:

• Neuroscience
• Pharmacology
• Radiochemistry

Background:

• The interplay between dopaminergic and cholinergic neurotransmission is crucial, particularly in conditions like Parkinson's disease.
• Positron emission tomography (PET) imaging offers a method to visualize and quantify neurotransmitter system dynamics in vivo.

Purpose of the Study:

• To investigate the impact of D2 receptor antagonists on the binding of [18F]-FEOBV to the vesicular acetylcholine transporter (VAChT) in rodent models.
• To assess the utility of [18F]-FEOBV PET imaging in quantifying changes in cholinergic activity under dopaminergic modulation.

Main Methods:

• Rodents were pretreated with haloperidol (D2/sigma antagonist), raclopride (selective D2 antagonist), or vehicle.
• Dynamic PET scans were acquired over 90 minutes following [18F]-FEOBV administration, with arterial blood sampling for input function.
• Net influx rate (Ki) was calculated using Patlak graphical analysis with metabolite-corrected plasma input function.

Main Results:

• Raclopride treatment non-significantly increased striatal Ki but significantly reduced cerebellar Ki, suggesting regional specificity.
• Haloperidol treatment led to a significant decrease in Ki across most brain regions, potentially indicating off-target binding or paradoxical effects.
• Plasma input functions and [18F]-FEOBV concentrations were largely unaffected by pretreatments, but haloperidol increased the parent fraction AUC.

Conclusions:

• Selective D2 receptor antagonism with raclopride can be partially quantified using [18F]-FEOBV PET imaging.
• Haloperidol's non-selective action complicates interpretation, suggesting potential binding to sigma receptors or other off-target effects.
• Further research is needed to elucidate the binding characteristics of [18F]-FEOBV at sigma receptors using selective ligands.