1. Positron Emission Tomography Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, U.S.A.
2. ^*Experimental Therapeutics Branch, National Institutes of Mental Health, Bethesda, Maryland, U.S.A.
3. ^†Clinical Brain Disorders Branch, National Institutes of Mental Health, Bethesda, Maryland, U.S.A.

Correspondence: Richard E Carson, PET Department, NIH, Building 10, Room 1C-401, 10 CENTER DR MSC 1180, Bethesda, MD 20892-1180, U.S.A.

Received 3 July 1996; Revised 18 October 1996; Accepted 23 October 1996.

Abstract

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.