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 (VT). Specific binding, calculated with three measures linearly proportional to the binding potential, demonstrated a 22-42% reduction in the postamphetamine study. VT 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 VT 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.
Carson
R E
RE
Positron Emission Tomography Department, National Institutes of Health, National Institutes of Mental Health, Bethesda, Maryland 20892-1180, USA.
Breier
A
A
de Bartolomeis
A
A
Saunders
R C
RC
Su
T P
TP
Schmall
B
B
Der
M G
MG
Pickar
D
D
Eckelman
W C
WC
D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism; D002250:Carbon Radioisotopes; D002531:Cerebellum / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000378:metabolism*; D007260:Infusion Pumps; D007262:Infusions, Intravenous; D008253:Macaca mulatta; D008954:Models, Biological; D020891:Raclopride; D012457:Salicylamides / Q000378:metabolism*; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D018492:Dopamine Antagonists; D012457:Salicylamides; D020891:Raclopride; D000661:Amphetamine; D004298:Dopamine