QUANTIFICATION OF AMPHETAMINE-INDUCED CHANGES IN [C-11] RACLOPRIDE BINDING WITH CONTINUOUS-INFUSION

Positron emission tomography and single photon emission computer tomog raphy receptor-binding ligands can be used to measure changes in neuro transmitter levels. In particular, amphetamine-induced dopamine releas e has been assessed with [C-11]raclopride by paired bolus injections a nd with [I-123]iodobenzamide by using a single bolus plus infusion (B/ I) study. Here, we measured the change in [C-11]raclopride-specific bi nding in rhesus monkeys after i.v. administration of 0.4 mg/kg ampheta mine 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 t he total distribution volume (V-T). Specific binding, calculated with three measures linearly proportional to the binding potential, demonst rated a 22-42% reduction in the postamphetamine study. V-T values from B/I studies were determined by the tissue-to-plasma ratio at equilibr ium, in addition to the bolus methods. There was good agreement betwee n the control V-T values between bolus and B/I studies. The amphetamin e-induced change in specific binding in B/I studies was 19 +/- 16%, me asured directly from tissue radioactivity levels. This study demonstra tes that stimulus-induced changes in specific binding can be measured with a single [C-11]raclopride study using the B/I method.