123I-Ioflupane/SPECT binding to striatal dopamine transporter (DAT) uptake in patients with Parkinson?s disease, multiple system atrophy, and progressive supranuclear palsy (original) (raw)
Related papers
Measurement of Dopamine Transporters in Parkinson's Disease
2000
Functional brain imaging targeting the presynaptic dopamine nerve terminal of the nigrostriatal system has been used for monitoring disease progression and evaluating therapeutic effectiveness in patients with Parkinson's disease (PD). 99m Tc-TRODAT-1 binds with high selectivity to the dopamine transporters in the striatum and can be imaged with SPECT 4 h after injection. We studied the test and retest reproducibility of 99m Tc-TRODAT-1 SPECT measures in patients with PD to assess the reliability of 99m Tc-TRODAT-1 for longitudinal evaluation of the nigrostriatal dopaminergic function. Methods: Each of 20 patients with PD underwent 2 99m Tc-TRODAT-1 SPECT scans at an interval of 2-3 wk. Patients were imaged 4 h after injection of 925 MBq 99m Tc-TRODAT-1. Two imaging outcome measures were evaluated: the ratio of specific-striatal-to-nonspecific uptake and the striatal asymmetry index. For both measures, the test/retest variability was calculated. Reproducibility of the 2 outcome measures was evaluated in terms of intraclass correlation coefficient (ICC) and 95% limits of agreement. Results: The mean ratio of specific-striatal-to-nonspecific uptake showed excellent test/retest reproducibility with a mean variability of 10.20%, an ICC of 0.95 (95% confidence interval ϭ 0.88 -0.98), and 95% limits of agreement, ranging from Ϫ0.19 to 0.19. The striatal asymmetry index had larger test/retest variability (60.41%), a slightly smaller ICC of 0.86 (95% confidence interval ϭ 0.65-0.95), and a wider range of 95% limits of agreement (Ϫ16.09 to 15.19). In addition, there was a significant negative correlation between the mean ratio of specific-striatal-to-nonspecific uptake and the motor subscore of the Unified Parkinson's Disease Rating Scale in both test and retest conditions. Conclusion: Our data indicate that the imaging outcome expressed by the mean ratio of specific-striatal-to-nonspecific uptake has an excellent test/retest reproducibility and correlates with disease severity. These findings suggest that 99m Tc-TRODAT-1 SPECT imaging is useful and feasible for measuring disease progression in PD.
Parkinsons disease and dopamine transporter neuroimaging: a critical review
Sao Paulo Medical Journal, 2006
Parkinson's disease (PD) is a common neurodegenerative disorder that is mainly caused by dopaminergic neuron loss in the substantia nigra. Several nuclear medicine radiotracers have been developed to evaluate PD diagnoses and disease evolution in vivo in PD patients. Positron emission tomography (PET) and single photon computerized emission tomography (SPECT) radiotracers for the dopamine transporter (DAT) provide good markers for the integrity of the presynaptic dopaminergic system affected in PD. Over the last decade, radiotracers suitable for imaging the DAT have been the subject of most efforts. In this review, we provide a critical discussion on the utility of DAT imaging for Parkinson's disease diagnosis (sensitivity and specifi city).
Dopamine transporter SPECT imaging in Parkinson’s disease and parkinsonian disorders
Turkish Journal of Medical Sciences, 2021
The dopamine transporter (DAT) imaging provides an objective tool for the assessment of dopaminergic function of presynaptic terminals which is valuable for the differential diagnosis of parkinsonian disorders related to a striatal dopaminergic deficiency from movement disorders not related a striatal dopaminergic deficiency. DAT imaging with single-photon emission computed tomography (SPECT) can be used to confirm or exclude a diagnosis of dopamine deficient parkinsonism in cases where the diagnosis is unclear. It can also detect the dopaminergic dysfunction in presymptomatic subjects at risk for Parkinson's disease (PD) since the reduced radiotracer binding to DATs in striatum is already present in the prodromal stage of PD. This review covers the rationale of using DAT SPECT imaging in the diagnosis of PD and other parkinsonian disorders, specifically focusing on the practical aspects of imaging and routine clinical indications.
PET imaging of the dopamine transporter in progressive supranuclear palsy and Parkinson's disease
Neurology, 1999
To differentiate the patterns of dopamine transporter loss between idiopathic PD and progressive supranuclear palsy (PSP). Methods: We used the radiotracer [ 11 C]-WIN 35,428 and PET. Regional striatal dopamine transporter binding was measured in the caudate, anterior putamen, and posterior putamen of six patients with L-dopa-responsive stage 2 PD, six patients with PSP, and six age-comparable healthy controls. Results: In patients with idiopathic PD, the most marked abnormality was observed in the posterior putamen (77% reduction), whereas transporter density in the anterior putamen (60% reduction) and the caudate (44% reduction) was less affected. Unlike the patients with PD, the PSP group showed a relatively uniform degree of involvement in the caudate (40% reduction), anterior putamen (47% reduction), and posterior putamen (51% reduction). When posterior putamen/caudate ratios were calculated, these values were significantly lower in patients with PD than they were in patients with PSP (p ϭ 0.0008) and the control group (p Ͻ 0.0001). Conclusions: Patients with PD have a more pronounced loss of dopamine transporters in the posterior putamen due to a subdivisional involvement of nigrostriatal dopaminergic projections in idiopathic PD. This technique is useful in the determination of neurochemical changes underlying PD and PSP, thus differentiating between them.
Assessing the integrity of the dopamine system in Parkinson's disease: How best to do it?
Movement Disorders, 2001
The recent identification of genetic defects associated with parkinsonism, coupled with advances in neurotransplantation and the possibility that neuroprotective strategies may become available, have elevated the importance of accurate quantitation of early damage to the nigrostriatal dopamine projection. In this issue of Movement Disorders, Yee et al. 1 describe the relationship between the uptake and decarboxylation of 6-[ 18 F]-fluoro-L-dopa (FD) as measured in vivo using positron emission tomography in N-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP)-treated monkeys, and nigral cell counts and striatal concentrations of dopamine and its metabolites. The authors found an excellent correlation between both uptake (K i ) and decarboxylation (k 3 ) of FD in the striatum and striatal levels of dopamine and its metabolites. However, although there was also a weaker correlation between striatal FD uptake and decarboxylation and nigral levels of these compounds, nigral dopamine cell counts did not correlate with either striatal levels of dopamine plus metabolites or with FD uptake/decarboxylation. In another recent paper from this group, 2 it was found that both uptake and decarboxylation as measured by positron emission tomography (PET) correlate with in vitro measures of decarboxylation, although there is an approximately 10-fold difference in the absolute values, which is not well understood.
Archives of Neurology, 2002
Background: Measuring progression of Parkinson disease (PD) using positron emission tomography may help demonstrate the efficacy of neuroprotective treatments. To date, 18 F-dopa has been the gold standard to measure presynaptic dopaminergic function in PD, but this tracer might overestimate the rate of neuronal death in PD because its uptake also depends on dopamine turnover rather than exclusively on the density of dopaminergic terminals in the striatum. The latter might be assessed using newly developed ligands of the membrane dopamine transporter.
Annals of Neurology, 1990
Using positron emission tomography (PET), we studied regional striatal **F-dopa uptake in 16 patients with L-doparesponsive Parkinson's disease (PD), 18 patients with multiple system atrophy, and 10 patients with progressive supranuclear palsy. Results were compared with those of 30 age-matched normal volunteers. The patients with PD showed significantly reduced mean uptake of "F-dopa in the caudate and putamen compared to controls, but while function in the posterior part of the putarnen was severely impaired (455% of normal), function in the anterior part of the putamen and in the caudate was relatively spared (62% and 84% of normal). Mean '*F-dopa uptake in the posterior putamen was depressed to similar levels in all patients. Unlike patients with PD, the patients with progressive supranuclear palsy showed equally severe impairment of mean "F-dopa uptake in the anterior and posterior putamen. Caudate 18F-dopa uptake was also significantly lower in patients with progressive supranuclear palsy than in patients with PD, being depressed to the same level as that in the putarnen. Mean "F-dopa uptake values in the anterior putamen and caudate in patients with multiple system atrophy lay between PD and progressive supranuclear palsy levels. Locomotor disability of individual patients with PD or multiple system atrophy correlated with decline in striatal "F-dopa uptake, but this was not the case for the patients with progressive supranuclear palsy. We conclude that patients with PD have selective nigral pathological features with relative preservation of the dopaminergic function in the anterior putamen and caudate, whereas there is progressively more extensive nigral involvement in multiple system atrophy and progressive supranuclear palsy. If an kinetic-rigid patient has equally depressed '*F-dopa uptake in the caudate and putamen, that person is likely to have neuropathological changes other than those of idiopathic PD.
Neurology, 1996
To determine the extent that different dopamine (DA) neuronal markers provide similar estimates of striatal (caudate and putamen) DA nerve terminal loss in idiopathic Parkinson's disease (PD), we compared, in postmortem striatum of 12 patients with PD and 10 matched controls, levels of five different DA neuronal markers.These markers included DA itself, three different estimates of the density of the DA transporter (DAT) ([sup 3 H]GBR 12,935 and [sup 3 H]WIN 35,428 binding; DAT protein immunoreactivity), and one estimate of the vesicular monoamine transporter (VMAT2; [sup 3 H]DTBZ binding). Striatal levels of all examined DA markers in PD were significantly intercorrelated. However, the magnitude of loss relative to controls was unequal (DAT protein = DA > [sup 3 H]WIN 35,428 > [sup 3 H]DTBZ > [sup 3 H]GBR 12,935), with the differences more marked in the severely affected putamen. The less severe reduction of binding of the DAT/VMAT2 radioligands relative to DA and DAT ...