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Measurement of Dopamine Release with Continuous Infusion of [¹¹C]Raclopride: Optimization and Signal-to-Noise Considerations

PET Department, Clinical Center, and Experimental Therapeutics Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland

Correspondence: For correspondence or reprints contact: Richard E. Carson, PhD, PET Department, National Institutes of Health, Bldg. 10, Rm. 1C-401, 10 Center Dr., MSC 1180, Bethesda, MD 20892-1180.

ABSTRACT

PET studies with [¹¹C]raclopride provide an indirect measure of changes in synaptic dopamine. Previously, we used the bolus-plus-infusion (B/I) method to assess dopamine response from the percentage change in binding potential (BP) before and after administration of amphetamine. The goal of this work is to optimize the measurement of changes in neurotransmitter with the B/I method by choosing the optimal timing for pre- and poststimulus scanning. Methods: Two sources of variability in BP were considered: within-subject and between-subject noise. A noise model based on a phantom study and human data was used to evaluate the within-subject noise. For between-subject noise, simulated time-activity curves were generated from measured [¹¹C]raclopride input functions. Optimal timing to measure BP was determined and applied to human data. Results: According to the simulation study, the optimal scan times for pre-and poststimulus scans were 39–50 and 58–100 min, respectively. The optimal timing resulted in a 28% noise reduction compared with the original timing. By applying the optimal timing to human studies, the statistical significance of the difference in BP between patients with schizophrenia and healthy volunteers increased from P = 0.038 to 0.012. Conclusion: Careful assessment of the sources of noise in receptor imaging studies can increase the sensitivity of the B/I method for the detection of biologic signals.

Key Words: [^l1C]raclopride • bolus/infusion • amphetamine • noise • optimization

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