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Imaging D2 receptor occupancy by endogenous dopamine in humans
M Laruelle1, C D D'Souza, R M Baldwin
1Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Summary
Endogenous dopamine significantly impacts D2 receptor measurements using SPECT. Acute dopamine depletion via AMPT increased binding potential, suggesting dopamine competition introduces errors but may allow synaptic dopamine estimation.
Area of Science:
- Neuroscience
- Radiopharmacology
- Medical Imaging
Background:
- Endogenous dopamine levels can influence in vivo D2 receptor imaging.
- Accurate quantification of D2 receptors is crucial for understanding neurological conditions.
Purpose of the Study:
- To evaluate the impact of endogenous dopamine on D2 receptor measurements in humans using SPECT.
- To assess if acute dopamine depletion can be used to estimate synaptic dopamine concentrations.
Main Methods:
- Single photon emission computerized tomography (SPECT) with [123I]IBZM was used.
- Acute dopamine depletion was induced using alpha-methyl-para-tyrosine (AMPT).
- Binding potential (BP) of [123I]IBZM was compared before and after AMPT administration.
Main Results:
- AMPT administration increased [123I]IBZM binding potential by 28% +/- 16%.
- Rodent studies indicated this was due to dopamine removal, not receptor upregulation.
- Estimated synaptic dopamine concentration was 45 +/- 25 nM.
Conclusions:
- Endogenous dopamine competition introduces significant variability in in vivo D2 receptor imaging (SPECT/PET).
- D2 receptor imaging combined with dopamine depletion may offer a method for estimating human brain synaptic dopamine levels.