A follow‐up study on 6‐[¹⁸F]fluoro‐L‐dopa uptake in early Parkinson's disease shows nonlinear progression in the putamen

Abstract

Sixteen subjects with de novo Parkinson's disease (PD) underwent three 6-[18F]fluoro-L-dopa (Fdopa) positron emission tomography (PET) scans during a follow-up time of 5 years (mean +/- SD 5.5 +/- 0.4 years) to study the progression of striatal dopaminergic hypofunction. Throughout the study, the smallest Fdopa uptake values were found in the dorso-caudal part of the putamen contralateral to the side with dominant motor symptoms. The rate of decline in Fdopa uptake in the contralateral putamen was faster in the beginning of the disease and slowed down as the disease progressed. The annual decline in Fdopa influx constant (Ki, unit x 10(-3) min(-1)) was on average 0.5 during the first 2 years and 0.2 during the subsequent 3 years (P = 0.002) in the contralateral putamen. In caudate, the rate of decline in Fdopa values was slower than in the putamen and did not change significantly during the follow-up time, annual decline in the contralateral caudate being 0.1 between baseline and 2 years and 0.3 between 2 and 5 years (P = 0.4). These results suggest that progression of putaminal dopaminergic hypofuncion in PD follows a nonlinear pattern at least in the contralateral side being faster in the beginning of the disease.

Advances in the Role of Neuroimaging to Monitor Disease Progression in Parkinson’s Disease

“…60 Autopsy studies in PD have shown a 45 % decrease in nigral cell counts during the first 10 years of PD, 10 times greater than the loss associated with normal aging, with a tendency to approach the normal age-related linear decline in the later stages. 5 53), but that at the same age of onset, the calculated preclinical durations are shorter when other tracers are used (13 years for DAT binding; six years for FD uptake, in keeping with other literature). 60 The sensitivity of imaging to detect preclinical dopaminergic dysfunction has been demonstrated in a number of high-risk groups, including asymptomatic individuals exposed to MPTP 63 and unaffected twins whose identical co-twins are affected.…”

Formation and development of Lewy pathology: a critical update

“…While the duration and severity of motor function, the corresponding decrease of dopamine, tyrosine hydroxylase (TH), dopamine transporter (DAT), and vesicular monoamine transporter-2 (VMAT-2) immunoreactivity in striatum are negatively correlated with total SN aSyn burden and neuronal loss [7,22,33,86], the latter shows no correlation with LB formation [54], and no relationship between LB stage and both clinical severity of PD (Hoehn and Yahr score) and age at death were found [15]. Progression of putaminal DAergic hypofunction (L-dopa uptake) shows a nonlinear pattern at least on the contralateral side being faster in early PD [13]. The proportion of LB-bearing SN cells appears to be stable over time, involving 3.6% of neurons in average, suggesting that, during the course of disease, the destruction of LBs may be equal to their production and that they are destroyed together with the afflicted neurons.…”

Objective and quantitative evaluation of motor function in a monkey model of Parkinson's disease

“…Specifically, positron emission tomography (PET) using 6-[ 18 F]-fluoro-3,4-dihydroxy-l-phenylalanine ([ 18 F]-F-DOPA), [ 11 C]-2␤-carbomethoxy-3␤-(4-fluorophenyl)-tropane ([ 11 C]-CFT), and [ 11 C]-raclopride has been clinically used to evaluate DA synthesis capacity, DA transporter (DAT), and DA receptors, respectively. Several PET studies in humans (Bruck et al, 2009;Nurmi et al, 2003;Rinne et al, 2001) and monkeys (Oiwa et al, 2003;Wullner et al, 1994) have demonstrated a behavior-related decrease in DA 0165-0270/$ -see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.jneumeth.2010.05.009 synthesis or DAT density in the striatum.…”