Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the rate of progression of striatal dopamine transporter function in Parkinson's disease (PD). Eight patients with early PD without antiparkinsonian medication and 7 healthy volunteers were investigated with [18F]CFT positron emission tomography (PET). The PET scan was carried out twice at an approximate 2-year interval. The uptake of [18F]CFT was calculated as a region-cerebellum:cerebellum ratio at 180 to 210 minutes after injection. At the first PET scan, the [18F]CFT uptake in PD patients in the putamen was 1.45 +/- 0.45 (mean +/- SD) (42% of the control mean) and 2.43 +/- 0.59 in the caudate nucleus (76% of the control mean). The ratios declined by the time of the second PET scan, and the rate of annual decline of the baseline mean in PD patients was 13.1% in the putamen and 12.5% in the caudate nucleus. In controls, the corresponding figures were 2.1% for the putamen and 2.9% for the caudate nucleus. The decline in [18F]CFT uptake was significantly higher in PD patients than in controls. Thus, dopamine transporter ligands such as [18F]CFT seem to be sensitive markers for the rate of progression in PD.
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PMID:Progression in Parkinson's disease: a positron emission tomography study with a dopamine transporter ligand [18F]CFT. 1085 47

The objective of this article was to study the reproducibility and effect of levodopa on dopamine transporter function measurements using 2beta-carbomethoxy-3beta-(4-[18F]fluorophenyl)tropane ([18F]CFT) positron emission tomography (PET). Seven de novo patients with Parkinson's disease (PD) were studied twice, before and after three months of levodopa medication. Eight healthy volunteer subjects participated in the reproducibility study. The [18F]CFT PET scan was done twice with an interval of approximately 2.5 months. The regions of interest (anterior and posterior putamen, caudate nucleus, and cerebellum) were drawn on individual magnetic resonance imaging (MRI) images, matched with the PET images, and copied onto the PET images. The [18F]CFT uptake was calculated as the region-cerebellum:cerebellum ratio at 180 to 210 minutes. Three-month levodopa treatment in PD patients had no significant effect on [18F]CFT uptake in any striatal subregion between the two PET scans. In PD patients, the percent change from baseline was 4.1% in the anterior putamen, 1.9% in the posterior putamen, and 4.0% in the caudate nucleus. No significant differences in [18F]CFT uptake between the first and second PET scan in any striatal subregion occurred in healthy controls. The intraclass correlation, indicating the reproducibility of the PET scan within subjects, was 0.94 for the anterior putamen, 0.86 for the posterior putamen, and 0.91 for the caudate nucleus. The percent change from baseline was 4.0% in the anterior putamen, 1.1% in the posterior putamen, and 2.8% in the caudate nucleus. Long-term levodopa treatment in PD patients had no effect on the [18F]CFT uptake in the striatum and the test-retest reproducibility was very high. These findings confirm [18F]CFT as a suitable ligand to monitor progression of PD.
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PMID:Reproducibility and effect of levodopa on dopamine transporter function measurements: a [18F]CFT PET study. 1108 35

The basal ganglia play a role in controlling movement during gait. The aim of the present study was to investigate changes in dopamine transporter (DAT) availability in the striatum and extrastriatal region in association with walking exercise in six normal subjects and seven age-matched unmedicated patients with Parkinson's disease. This was done by comparing DAT radioligand uptake in the dopaminergic projection areas after gait with that under the resting condition using a DAT probe, 11C-labelled 2-beta-carbomethoxy-3beta-(4-fluorophenyl) tropane ([11C]CFT) and PET. Physiological parameters were stable during and after gait in both groups. The regions of interest method for measuring differences in [11C]CFT uptake level and voxel-based statistical parametric mapping (SPM96) showed that [11C]CFT uptake in the striatum (specifically the putamen) was decreased by gait to a greater extent in normal subjects, whereas a significant reduction in [11C]CFT uptake was not found in the putamen but in the caudate and orbitofrontal cortex in Parkinson's disease patients. These results are the first in vivo evidence that DAT availability is reduced in the nigrostriatal projection area by basic human behaviour, i.e. gait. Alterations in this availability in Parkinson's disease suggested that shifted activation in the medial striatum and the mesocortical dopaminergic system might reflect the pathophysiology of parkinsonian gait.
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PMID:Changes in dopamine availability in the nigrostriatal and mesocortical dopaminergic systems by gait in Parkinson's disease. 1128 77

The aim of this study was to compare two PET ligands, 6-[(18)F]fluoro-L-dopa ([(18)F]FDOPA) and (18)F-labeled CFT, 2beta-carbomethoxy-3beta-(4-[(18)F]-fluorophenyl)tropane ([(18)F]CFT), in detecting presynaptic dopaminergic hypofunction in early Parkinson's disease (PD). These ligands reflect different aspects of presynaptic dopaminergic function, since [(18)F]FDOPA mainly reflects 6-[(18)F]fluorodopamine (fluorodopamine) synthesis and storage whereas [(18)F]CFT uptake is related to dopamine transporter function. Eight de novo patients with PD who had never been on antiparkinsonian medication were investigated with [(18)F]FDOPA and [(18)F]CFT PET. Five healthy volunteers were studied as controls. In PD patients, both [(18)F]FDOPA and [(18)F]CFT uptakes were significantly reduced both in the contralateral and ipsilateral anterior and posterior putamen. The reduction was greatest in the contralateral posterior putamen (to 28% of control mean for [(18)F]FDOPA, P < 0.0001 and to 16% for [(18)F]CFT, P < 0.0001). Individually, all patients' [(18)F]FDOPA and [(18)F]CFT uptake values in the contralateral anterior and posterior putamen were below 3 SD of the control mean. In the caudate nucleus, the mean uptake of both tracers was significantly reduced both ipsilaterally and contralaterally, but less severely than in the putamen (to 69% of the control mean for [(18)F]FDOPA, P = 0.003 and to 60% for [(18)F]CFT, P = 0.001 contralaterally). Our results show that both [(18)F]FDOPA as well as [(18)F]CFT sensitively detect presynaptic dopaminergic hypofunction in early PD. They demonstrate a considerable reduction of tracer uptake that is greatest in the posterior putamen, followed by the anterior putamen and the caudate nucleus.
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PMID:[(18)F]FDOPA and [(18)F]CFT are both sensitive PET markers to detect presynaptic dopaminergic hypofunction in early Parkinson's disease. 1130 57

We investigated the microglial response to progressive dopamine neuron degeneration using in vivo positron emission tomography (PET) imaging and postmortem analyses in a Parkinson's disease (PD) rat model induced by unilateral (right side) intrastriatal administration of 6-hydroxydopamine (6-OHDA). Degeneration of the dopamine system was monitored by PET imaging of presynaptic dopamine transporters using a specific ligand (11)C-CFT (2beta-carbomethoxy-3beta-(4-fluorophenyl) tropane). Binding of (11)C-CFT was markedly reduced in the striatum indicating dopaminergic degeneration. Parallel PET studies of (11)C-PK11195 (1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3 isoquinoline carboxamide) (specific ligand for activated microglia) showed increased binding in the striatum and substantia nigra indicative of a microglial response. Postmortem immunohistochemical analyses were performed with antibodies against CR3 for microglia/macrophage activation. Using a qualitative postmortem index for microglial activation we found an initially focal, then widespread microglial response at striatal and nigral levels at 4 weeks postlesion. These data support the hypothesis that inflammation is a significant component of progressive dopaminergic degeneration that can be monitored by PET imaging.
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PMID:Neuroinflammation of the nigrostriatal pathway during progressive 6-OHDA dopamine degeneration in rats monitored by immunohistochemistry and PET imaging. 1191 59

[(11)C]CFT and[(11)C]raclopride images obtained by positron emission tomography (PET) are used to evaluate pre-synaptic dopamine transporter availability and post-synaptic dopamine D(2) receptor binding, respectively. A combined study with these tracers is useful for the differential diagnosis of Parkinson's disease. We generated three-dimensional (3D) animations of striatum PET images for the diagnosis of Parkinson's disease. Brain images of a normal subject and a typical Parkinson's disease patient with[(11)C]CFT and[(11)C]raclopride were obtained using a PET camera. Three-dimensional animations were generated from serial maximum intensity projection (MIP) images created by gradually changing the projection angle. Furthermore, the striatum images extracted from brain data were superimposed over a brain surface magnetic resonance (MR) image that was created by the volume-rendering method, and 3D animations were similarly generated. The present 3D animations were clinically useful for the differential diagnosis of brain diseases, because we were able to observe distributions of[(11)C]CFT and[(11)C]raclopride from any angle and to grasp at a glance the regional differences of distributions in reference to anatomical landmarks.
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PMID:[Three-dimensional projection display of striatum dopamine function measured by PET]. 1257 15

The aim of this study was to investigate the progression of dopaminergic hypofunction in striatal subregions in Parkinson's disease (PD). We studied 12 patients with early PD and 11 healthy controls with a dopamine transporter ligand 2beta-carbomethoxy-3beta-(4-[(18)F]-fluorophenyl)tropane ([(18)F]CFT) positron emission tomography (PET). The PET scan was carried out twice with an average interval of 2.2 years. The regions of interest (anterior and posterior putamen, caudate nucleus, and cerebellum) were drawn on individual magnetic resonance imaging (MRI) images, matched with the PET images, and copied onto the PET images. At the first PET scan in PD patients, the [(18)F]CFT uptake in the anterior putamen was 1.92 +/- 0.67, which was 45% of the control mean, and in the posterior putamen 1.02 +/- 0.55, being only 27% of the control mean. For the caudate nucleus the corresponding figure was 2.55 +/- 0.58 (71% of the control mean). The uptake ratios had declined significantly by the time of the second PET scan and the absolute annual rate of decline of the tracer uptake was 0.23 +/- 0.14 (P < 0.001) in the anterior putamen, 0.13 +/- 0.13 (P = 0.005) in the posterior putamen, and 0.20 +/- 0.15 (P < 0.001) in the caudate nucleus. There was a statistically significant difference of the decline in the tracer uptake between the anterior and posterior putamen (P = 0.033). When the rate of progression was calculated compared to the normal control mean, the rate of annual decline was 5.3% in the anterior putamen, 3.3% in the posterior putamen, and 5.6% in the caudate nucleus, without significant changes among striatal subregions (P = 0.10). When ipsi- and contralateral sides were analyzed separately, the absolute decline of [(18)F]CFT uptake in the putamen was higher in the side ipsilateral to the predominant symptoms than in the contralateral side (P = 0.035 for anterior putamen and P = 0.026 for posterior putamen). In the caudate nucleus the absolute decline was not different between ipsi- and contralateral sides (P = 0.76). In healthy controls, no significant decline of [(18)F]CFT uptake was detected. The results are suggestive of slower progression in the posterior putamen, where the disease is more advanced, but studies to follow up the same patient at several time points are needed to resolve this question. Synapse 48:109-115, 2003.
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PMID:Progression of dopaminergic hypofunction in striatal subregions in Parkinson's disease using [18F]CFT PET. 1264 35

Neurophysiological studies of the brain in normal and Parkinson's disease (PD) patients have indicated intricate connections for basal ganglia-induced control of signaling into the motor cortex. To investigate if similar mechanisms are controlling function in the primate brain (Macaca fascicularis) after MPTP-induced neurotoxicity, we conducted PET studies of cerebral blood flow, oxygen and glucose metabolism, dopamine transporter, and D2 receptor function. Our observations after MPTP-induced dopamine terminal degeneration of the caudate and putamen revealed increased blood flow (15%) in the globus pallidus (GP), while blood flow was moderately decreased (15-25%) in the caudate, putamen, and thalamus and 40 % in the primary motor cortex (PMC). Oxygen extraction fraction was moderately increased (10-20%) in other brain areas but the thalamus, where no change was observable. Oxygen metabolism was increased in the GP and SMA (supplementary motor area including premotor cortex, Fig. 3) by a range of 20-40% and decreased in the putamen and caudate and in the PMC. Glucose metabolism was decreased in the caudate, putamen, thalamus, and PMC (range 35-50%) and enhanced in the GP by 15%. No change was observed in the SMA. In the parkinsonian primate, [(11)C]CFT (2beta-carbomethoxy-3beta-(4-fluorophenyltropane) dopamine transporter binding was significantly decreased in the putamen and caudate (range 60-65%). [(11)C]Raclopride binding of dopamine D(2) receptors did not show any significant changes. These experimental results obtained in primate studies of striato-thalamo-cortico circuitry show a similar trend as hypothetized in Parkinson's disease-type degeneration.
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PMID:Mapping of brain function after MPTP-induced neurotoxicity in a primate Parkinson's disease model. 1456 76

In order to characterize the sensitivity of an analog of levodopa and a dopamine transporter ligand to detect defects in nigrostriatal function, the uptake of [(18)F]FDOPA and [(18)F]CFT was studied ex vivo in a rat model of Parkinson's disease. The brains of these rats were unilaterally lesioned with an intranigral injection of 6-hydroxydopamine. The lesioned animals were divided into three groups subject to their behavior after pharmacological challenges. Circling behavior was recorded after amphetamine, apomorphine, and L-DOPA challenge in order to predict lesion size. The spatial distribution of radioactivity after [(18)F]FDOPA or [(18)F]CFT injection in brain sections was determined with digital autoradiography. Regions of interest were left/right striatum, left/right substantia nigra, and cerebellum. The degree of unilateral lesion for each animal was confirmed by counting of nigral tyrosine hydroxylase-positive cell bodies. With both tracers the uptake in the lesioned side was lower than in the intact side in the striatum and in the substantia nigra. In conclusion, both tracers clearly demonstrated nigrostriatal dopaminergic hypofunction and correlated with the number of nigral dopaminergic neurons. However, [(18)F]FDOPA showed a much higher unspecific uptake of radioactivity, due to extensive metabolism; therefore, this tracer was less sensitive than the transporter tracer [(18)F]CFT to detect these defects.
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PMID:Uptake of 6-[18F]fluoro-L-dopa and [18F]CFT reflect nigral neuronal loss in a rat model of Parkinson's disease. 1461 79

We investigated the integrity of striatal dopaminergic system in seven patients with dopa-responsive dystonia (DRD). Dopamine transporter function ([(11)C]CFT) and D1 ([(11)C]NNC 756) and D2 receptors ([(11)C]raclopride) were studied in same patients using positron emission tomography. Compared to age-adjusted control values the dopamine D2 receptor availability was increased in DRD. The mean age-adjusted [(11)C]raclopride uptake was 116% of the control mean in the putamen (p = 0.004) and 114% in the caudate nucleus (p = 0.007). The mean [(11)C]NNC 756 uptake was not different between DRD patients and controls, the age-adjusted uptake in DRD being 93% of mean control value in the putamen (p = 0.20) and 95% in the caudate nucleus (p = 0.40). The dopamine transporter binding was not altered. The [(11)C]CFT uptake in DRD was 96% of the control value in the putamen (p = 0.64), and 95% in the caudate nucleus (p = 0.44). In conclusion, striatal dopamine D2 receptors availability is increased in DRD whereas dopamine D1 receptors and dopamine transporter ligand binding is unchanged. The pattern of changes in striatal dopaminergic system in DRD is different from that reported in juvenile Parkinson's disease. The increased D2 receptor availability may be due to reduced competition by endogenous dopamine or a compensatory response to dopamine deficiency, or both.
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PMID:Striatal dopaminergic system in dopa-responsive dystonia: a multi-tracer PET study shows increased D2 receptors. 1471 16


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