Effect of amphetamine on [¹⁸F]fallypride in vivo binding to D₂ receptors in striatal and extrastriatal regions of the primate brain: Single bolus and bolus plus constant infusion studies

[¹⁸F]fallypride is a new positron emission tomography (PET) dopamine D₂ receptor radiotracer that provides visualization of D₂ receptors in both striatal and extrastriatal areas. Here, the vulnerability of [¹⁸F]fallypride binding to endogenous dopamine (DA) levels was evaluated by examining the effect of amphetamine on [ ¹⁸F]fallypride binding in striatal and extrastriatal regions. Data were acquired in three male baboons at three different doses of i.v. amphetamine, using two different [¹⁸F]fallypride administration protocols (single bolus and bolus plus constant infusion). Scans were performed following a single bolus of [¹⁸F]fallypride under control conditions and following 1 mg/kg i.v. amphetamine and with an [¹⁸F]fallypride bolus plus constant infusion design under control, 0.5 mg/kg, and 0.3 mg/kg amphetamine i.v. conditions. Significant decreases in [¹⁸F]fallypride binding potential were seen in striatum (-49%, -18%, and -14%), thalamus (-25%, -23%, and -14%), and hippocampus (-36%, -24%, and -12%) following 1 mg/kg, 0.5 mg/kg, and 0.3 mg/kg doses of amphetamine, respectively. Additional analyses were performed suggesting that these results were not artifacts of nonreceptor-related effects such as regional flow changes or partial volume effects. In conclusion, [¹⁸F]fallypride binding is vulnerable to endogenous competition by DA in striatum as well as extrastriatal regions, suggesting that this ligand may be suitable for the study presynaptic DA function in striatal and extrastriatal areas.