Limitations of SRTM, Logan graphical method, and equilibrium analysis for measuring transient dopamine release with [(11)C]raclopride PET

Conventional PET methods to estimate [(11)C]raclopride binding potential (BP ND) assume that endogenous dopamine concentration does not change during the scan time. However, this assumption is purposely violated in studies using pharmacological or behavioral stimuli to invoke acute dopamine release. When the assumption of steady-state dopamine is violated, conventional analysis methods may produce biased or even unusable estimates of BP ND. To illustrate this problem, we examined the effect of scan duration on ΔBP ND estimated by three common analysis methods (simplified reference tissue model, Logan graphical reference method, and equilibrium analysis) applied to simulated and experimental single-scan activation studies. The activation - dopamine release - in both the simulated and experimental studies was brief. Simulations showed ΔBP ND to be highly dependent on the window of data used to determine BP ND in the activation state. A similar pattern was seen in the data from human smoking studies. No such pattern of ΔBP ND dependence on the window of data used was apparent in simulations where dopamine was held constant. The dependence of ΔBP ND on the duration of data analyzed illustrates the inability of conventional methods to reliably quantify short-lived increases in endogenous dopamine.