Initial Comparison of ntPET with Microdialysis Measurements of Methamphetamine-Induced Dopamine Release in Rats: Support for Estimation of Dopamine Curves from PET Data

Abstract

A recently introduced mathematical method for extracting temporal characteristics of neurotransmitter release from dynamic positron emission tomography (PET) data was tested. The method was developed with the hope that by uncovering temporal information about neurotransmitter (nt) dynamics in PET data, researchers could shed new light on mechanisms of psychiatric diseases such as drug abuse and its treatment. In this study, we apply our model-based method, "ntPET", to (11)C-raclopride PET scans of rats in which the dopaminergic response to a microinfusion of methamphetamine in one striatum was assayed simultaneously by microdialysis and PET. Uptake of (11)C-raclopride into the untreated contralateral striatum was used as an input to the ntPET model. Direct comparisons of the model-based ntPET analysis and the microdialysis measurements confirmed that ntPET produced dopamine curves that were very similar in timing (takeoff and peak times) to the microdialysis curves. Variances in takeoff and peak times were comparable for the two methods. Neither method detected a false dopamine response to drug in a control animal. The high degree of correspondence between ntPET estimates and microdialysis measurements lends strong support to the idea that temporal information regarding dopamine release exists in dynamic (11)C-raclopride PET data and that it can be estimated reliably via ntPET. The method is entirely translatable to human PET imaging.