Quantification of amphetamine-induced changes in [11C]raclopride binding with continuous infusion

Positron emission tomography and single-photon emission computer tomography receptor-binding ligands can be used to measure changes in neurotransmitter levels. In particular, amphetamine-induced dopamine release has been assessed with [¹¹C]raclopride by paired bolus injections and with [¹²³I]iodobenzamide by using a single bolus plus infusion (B/I) study. Here, we measured the change in [¹¹C]raclopride-specific binding in rhesus monkeys after i.v. administration of 0.4 mg/kg amphetamine by using both the bolus and B/I paradigms. Paired bolus studies (control and postamphetamine) were analyzed using compartment modeling and graphical analysis with a new plasma metabolite model to measure the total distribution volume (V(T)). Specific binding, calculated with three measures linearly proportional to the binding potential, demonstrated a 22-42% reduction in the postamphetamine study. V(T) values from B/I studies were determined by the tissue-to-plasma ratio at equilibrium, in addition to the bolus methods. There was good agreement between the control V(T) values between bolus and B/I studies. The amphetamine-induced change in specific binding in B/I studies was 19 ± 16%, measured directly from tissue radioactivity levels. This study demonstrates that stimulus-induced changes in specific binding can be measured with a single [¹¹C]raclopride study using the B/I method.