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.

Creating Dynamic Images of Short-lived Dopamine Fluctuations with lp-ntPET: Dopamine Movies of Cigarette Smoking

“…These models have been validated against a gold standard. Specifically, we have demonstrated that our models predict dopamine concentrations over time from PET data in rats that are in good agreement with simultaneously acquired microdialysis measurements 4,7 . Advantages : The most recent of our models have been either linear and non-parametric (np-ntPET) 1 or linear and parametric (lp-ntPET) 7 .…”

“…The result of doing so is a dopamine movie like the ones presented herein. Key aspects of our methods for estimating the dopamine transients in PET data have been validated previously: in rats undergoing simultaneous PET and microdialysis 4 and in humans performing a finger tapping task 3,4 .…”

Imaging DA release in a rat model of L-DOPA-induced dyskinesias: A longitudinal in vivo PET investigation of the antidyskinetic effect of MDMA

“…DA competes with [ 11 C] raclopride for the same binding site on the D 2 /D 3 receptor and displaces the radioligand due to its higher affinity for the receptor. This competition was found to be linearly related to the amount of DA after a pharmacological challenge with amphetamine in simultaneous PET/ microdialysis experiments in primates Endres et al, 1997;Hartvig et al, 1997;Laruelle, 2000;Morris et al, 2008;Tsukada et al, 1999).…”

A systematic microdialysis study of dopamine transmission in the accumbens shell/core and prefrontal cortex after acute antipsychotics

“…In order to fill this gap, we decided to embark in a systematic comparative microdialysis study of the acute effects of AP on extracellular DA in the NAc shell and core and medial prefrontal cortex (PFCX). Such a study might have predictive translational value, due to the high degree of concordance between microdialysis and PET as a means to monitor extracellular DA dynamics in specific brain areas (Morris et al 2008;Narendran et al 2014).…”