Dopamine Storage Capacity in Caudate and Putamen of Patients with Early Parkinson's Disease: Correlation with Asymmetry of Motor Symptoms

Abstract

Conventional graphical analysis of positron emission tomography (PET) recordings of the cerebral uptake of the DOPA decarboxylase substrate [ 18 F]fluorodopa (FDOPA) assumes irreversible trapping of [ 18 F]fluorodopamine formed in the brain. However, 4-h long PET recordings allow the estimation of a rate constant for elimination of [ 18 F]fluorodopamine from the brain (k loss ), from which can be calculated an effective distribution volume (EDV 1 ), which is an index of [ 18 F]fluorodopamine storage capacity. We earlier developed a method employing 2-h long FDOPA recordings for the estimation of k loss and EDV, here defined as EDV 2 . This method is based on subtraction of the calculated brain concentrations of the FDOPA metabolite O-methyl-FDOPA, rather than the subtraction of the entire radioactivity in a reference region. We now extend this method for the parametric mapping of these parameters in the brain of healthy aged volunteers and patients with Parkinson's disease (PD), with asymmetry of motor symptoms. For parametric mapping, we use a novel application of a multilinear solution for the two-tissue compartment FDOPA model. We also test a new application of the Logan graphical analysis for mapping of the FDOPA distribution volume at equilibrium. The estimates of k loss and EDV 2 were more sensitive for the discrimination of biochemical abnormality in the putamen of patients with early PD relative to healthy aged subjects, than was the conventional net influx estimate. Of the several methods, multilinear estimates of EDV 2 were most sensitive for discrimination of PD and normal putamen. However, k loss was most sensitive for detecting biochemical asymmetry in the putamen of PD patients, and only k loss also detected in the caudate of PD patients a decline in the retention of [ 18 F]fluorodopamine relative to healthy aged control subjects.

Inflammation Effects on Motivation and Motor Activity: Role of Dopamine

“…Increased uptake and decreased turnover of FDOPA in the basal ganglia following IFN-α administration are in stark contrast to that observed in patients with PD, where decreased uptake and increased FDOPA turnover are seen. Decreased uptake of FDOPA in PD is believed to be a function of the loss of DAergic neurons and/or their projections throughout the basal ganglia (Kaasinen et al, 2001;Kumakura and Cumming, 2009;Leenders et al, 1986), and intact or increased turnover suggests that the surviving neurons are capable of normal release (Kumakura and Cumming, 2009;Kumakura et al, 2006). Increased FDOPA uptake during IFN-α treatment suggests intact terminals that exhibit a potential depletion of DA and increased synthetic capacity.…”

Cytokine effects on the basal ganglia and dopamine function: The subcortical source of inflammatory malaise

“…Increased uptake and decreased turnover of FDOPA in the basal ganglia following IFN-alpha administration is in stark contrast to that observed in patients with PD where decreased uptake and increased FDOPA turnover is found. Decreased uptake of FDOPA in PD is believed to be a function of loss of dopaminergic neurons and/or their projections throughout the basal ganglia [95, 111, 116], and intact or increased turnover suggests that the surviving neurons are capable of normal release [111, 112]. Increased FDOPA uptake during IFN-alpha treatment suggests a potential depletion of dopamine and increased synthetic capacity.…”

Creativity in Parkinson's disease as a function of right versus left hemibody onset

“…Other investigators have reported a greater reduction in striatal dopamine transporter binding contralateral to the more affected side of the body [15][16][17]. Further, the putamen and caudate contralateral to the more affected side of the body are associated with a reduced [ 18 F] dopa effective distribution volume and elimination rate [18]. Even when patients who had unilateral onset develop bilateral signs and symptoms these patients' motor and neuropathological asymmetries persist [19], with more severe extrapyramidal signs on the side of the body initially affected [20].…”