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Quantification of amphetamine-induced changes in [11C]raclopride binding with continuous infusion
R E Carson1, A Breier, A de Bartolomeis
1Positron Emission Tomography Department, National Institutes of Health, National Institutes of Mental Health, Bethesda, Maryland 20892-1180, USA.
Summary
Positron emission tomography (PET) studies show amphetamine reduces dopamine receptor binding. A new bolus plus infusion (B/I) method allows accurate measurement in a single [11C]raclopride scan, simplifying dopamine release assessment.
Area of Science:
- Neuroscience
- Radiochemistry
- Pharmacology
Background:
- Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) enable neurotransmitter level assessment.
- Dopamine release, particularly amphetamine-induced, is studied using ligands like [11C]raclopride and [123I]iodobenzamide.
Purpose of the Study:
- To measure changes in [11C]raclopride-specific binding after amphetamine administration in rhesus monkeys.
- To compare the bolus injection and bolus plus infusion (B/I) paradigms for assessing dopamine release.
Main Methods:
- Rhesus monkeys received intravenous amphetamine (0.4 mg/kg).
- [11C]raclopride binding was assessed using both paired bolus injections and a single B/I study.
- Compartment modeling, graphical analysis, and a plasma metabolite model were used to determine total distribution volume (VT).
Main Results:
- Specific binding showed a 22-42% reduction post-amphetamine with the bolus method.
- The B/I method yielded a 19 +/- 16% amphetamine-induced change in specific binding.
- Good agreement was observed for VT values between bolus and B/I control studies.
Conclusions:
- The bolus plus infusion (B/I) method accurately measures stimulus-induced changes in specific binding.
- A single [11C]raclopride B/I study can effectively assess amphetamine-induced dopamine release.
- The B/I method offers a more efficient approach compared to paired bolus injections.