Measurement of dopamine release with continuous infusion of [C-11]raclopride: Optimization and signal-to-noise considerations

PET studies with [C-11]raclopride provide an indirect measure of changes in synaptic dopamine. Previously, we used the bolus-plus-infusion (B/I) metho d to assess dopamine response from the percentage change in binding potenti al (Delta BP) before and after administration of amphetamine. The goal of t his work is to optimize the measurement of changes in neurotransmitter with the B/I method by choosing the optimal timing for pre- and poststimulus sc anning. Methods: Two sources of variability in Delta BP were considered: wi thin-subject and between-subject noise. A noise model based on a phantom st udy and human data was used to evaluate the within-subject noise. For betwe en-subject noise, simulated time-activity curves were generated from measur ed [C-11]raclopride input functions. Optimal timing to measure bBP was dete rmined and applied to human data. Results: According to the simulation stud y, 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 reductio n compared with the original timing. By applying the optimal timing to huma n studies, the statistical significance of the difference in Delta BP betwe en patients with schizophrenia and healthy volunteers increased from P = 0. 038 to 0.012. Conclusion: careful assessment of the sources of noise in rec eptor imaging studies can increase the sensitivity of the B/I method for th e detection of biologic signals.