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)

Previous studies have utilized single-photon emission computed tomography (SPECT) to demonstrate decreased [123I]beta-CIT striatal uptake in idiopathic Parkinson disease (PD) patients. The present study extends this work by examining SPECT outcome measures in a larger group of PD patients with varying disease severity. Twenty-eight L-dopa-responsive PD patients (Hoehn-Yahr stages 1-4) and 27 healthy controls had SPECT scans at 18 to 24 hours after injection of [123I]beta-CIT. Specific to nondisplaceable striatal uptake ratios (designated V3") were correlated with Hoehn-Yahr stage and Unified Parkinson's Disease Rating Scale (UPDRS) subscores. Linear discriminant function analyses utilizing striatal uptakes, putamen-to-caudate ratios, and ipsilateral-contralateral asymmetry indices were performed. Decreased striatal tracer uptake (V3") was correlated with total UPDRS score for both contralateral and ipsilateral striatum. Putamen uptake was relatively more reduced than caudate with mean putamen:caudate ratios of 0.50 +/- 0.17 and 0.82 +/- 0.09 for PD patients and controls, respectively. Ipsilateral:contralateral asymmetry was significantly greater in PD patients than controls. Discriminant function analysis utilizing V3" for ipsilateral and contralateral caudate and putamen correctly classified all 55 cases. These data demonstrate marked differences in [123I]beta-CIT SPECT measures in healthy controls and PD patients. The significant correlation of SPECT measures with motor severity suggests [123I]beta-CIT may be a useful marker of disease severity in PD.
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PMID:Decreased single-photon emission computed tomographic [123I]beta-CIT striatal uptake correlates with symptom severity in Parkinson's disease. 757 55

beta-CIT (2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane) is a new ligand that has a high affinity to dopamine and serotonin re-uptake sites. [123I] beta-CIT was prepared by reacting the corresponding trimethylstannyl precursor with no-carrier-added 123I. Iodogen was used as an oxidizing agent. The labeling mixture was purified by filtration through a mini-column. The purity of the product was confirmed by analytical HPLC. The total radiochemical yield was 67 +/- 5%. The radiochemical purity was > 95% and the specific activity was > 107 GBq/mol (> 2900 Ci/mmol). The final product was confirmed to be free of endotoxins before intravenous administration. Two healthy male volunteers were injected iv with 120-160 MBq of [123I] beta-CIT and scanned with a 3-head gamma-camera (Siemens MultiSPECT3). Dynamic SPECT scans were performed for up to 2 hours. There was a high accumulation of radioactivity in the striatum and in the thalamus, and some in the medial prefrontal area. Thus, we have developed an easy method to prepare [123I] beta-CIT with a high specific radioactivity and in a sufficient radiochemical yield. Specific [123I] beta-CIT binding in striatal and thalamic regions was demonstrated in humans. [123I] beta-CIT is a potential marker of the dopamine and serotonin transporters and can be used to study the pathophysiology of Parkinson's disease, as well as neuropsychiatric disorders.
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PMID:[123I] beta-CIT, a tracer for dopamine and serotonin re-uptake sites: preparation and preliminary SPECT studies in humans. 763 56

Single photon emission computerized tomography (SPECT) studies in non-human primates have previously shown that the cocaine derivative [123I]-2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane ([123I]beta-CIT) labels dopamine transporters in the striatum and serotonin transporters in the hypothalamus-midbrain area. Here, we report on the regional kinetic uptake of [123I]beta-CIT in the brain of 4 normal volunteers and 2 patients with Parkinson's disease. In healthy subjects striatal activity increased slowly to reach peak values at about 20 hours post injection. In the hypothalamus-midbrain area peak activities were observed at about 4 hours with a slow decrease thereafter. Low activity was observed in cortical and cerebellar areas. The striatal to cerebellar ratio was about 4 after 5 hours and 9 after 20 hours. In 2 patients with idiopathic Parkinson's disease striatal activity was markedly decreased while the activity in hypothalamus-midbrain areas was only mildly diminished. Uptake into cortical and cerebellar areas appeared to be unchanged in Parkinson's disease. Consequently, in Parkinson's disease the striatal to cerebellar ratio was decreased to values around 2.5 after 20 hours. These preliminary methodological studies suggest that [123I]beta-CIT is a useful SPECT ligand for studying dopamine and possibly also serotonin transporters in the living human brain.
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PMID:SPECT imaging of dopamine and serotonin transporters with [123I]beta-CIT. Binding kinetics in the human brain. 811 Apr 40

The iodinated cocaine analogue 2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane ([123I]beta-CIT), a new dopamine transporter, was preliminary tested in human brain. Two normal volunteers and two patients with Parkinson's disease were imaged with a high-resolution single-photon emission tomography scanner. The specific binding of [123I]beta-CIT in the basal ganglia and thalamus was high in normal volunteers. In addition, there was relatively intense uptake in the medial prefrontal area. Patients with Parkinson's disease who were older than controls showed significantly lower specific binding in the basal ganglia and thalamus and no uptake in the medial prefrontal cortex. This decrease in the dopamine transporter may be age related.
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PMID:Initial experience with single-photon emission tomography using iodine-123-labelled 2 beta-carbomethoxy-3 beta-(4-iodophenyl) tropane in human brain. 822 73

[123I][(1R)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane] ([123I]beta-CIT) labels dopamine transporters and is, therefore, a marker of neurons that degenerate in Parkinson disease. Single photon emission computed tomography imaging with [123I]beta-CIT showed that radioactivity in striatal regions in healthy subjects increased during a 2-day imaging study, whereas that in Parkinsonian patients peaked earlier at reduced levels relative to healthy subjects. Kinetic analyses of radioactivity in plasma and brain suggest that this decrease was due to an approximately 65% loss of target sites in patients compared with healthy subjects; greater losses occurred in putamen than in caudate. All patients showed lateralized differences in striatal uptake, with greater losses in the striatum contralateral to the side of the body with initial symptoms. These preliminary results suggest that [123I]beta-CIT is a marker for the loss of striatal dopamine terminals in patients with Parkinson disease. Single photon emission computed tomographic imaging with [123I]beta-CIT may be useful for early diagnosis of the disorder, for monitoring the progression of the disease, and for distinguishing the idiopathic disorder from other Parkinsonian syndromes with more widespread pathology.
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PMID:Single photon emission computed tomographic imaging demonstrates loss of striatal dopamine transporters in Parkinson disease. 826 56

We have used in vivo single-photon emission computed tomography (SPECT) of the dopamine transporter with 2 beta-carboxymethoxy-3 beta-(4-iodophenyl)tropane ([123I] beta-CIT) to investigate striatal dopamine transporter loss in patients with early Parkinson's disease (PD). Striatal uptake of ([123I] beta-CIT was compared in eight early-PD patients with exclusively hemi-parkinsonism and eight age- and sex-matched healthy subjects. [123I] beta-CIT striatal uptake was reduced by approximately 53% contralateral and by 38% ipsilateral to the clinically symptomatic side in the hemi-PD patients, compared with the mean striatal uptake in age- and sex-matched healthy subjects. The relative reduction in [123I] beta-CIT uptake in the hemi-PD patients was greater in the putamen than in the caudate. These data demonstrate that SPECT imaging of the dopamine transporter with [123I] beta-CIT can identify patients with PD at the onset of motor symptoms and suggest that this technique also may be useful in identifying individuals with developing dopaminergic pathology before onset of motor symptoms.
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PMID:[123I] beta-CIT/SPECT imaging demonstrates bilateral loss of dopamine transporters in hemi-Parkinson's disease. 855 82

The monoamine transporter was studied in 4 healthy controls and 5 patients with early Parkinson's disease (PD), who had not received any antiparkinsonian medication, by means of positron emission tomography (PET) using two novel ligands, [11C]beta-CIT and [11C]beta-CFT. Both ligands showed highest uptake in the striatum. There was intermediate accumulation of activity in the thalamus and midbrain, which was more marked for [11C]beta-CIT than for [11C]beta-CFT. In the cortical areas, uptake of both ligands was not different from that seen in the cerebellum. In the controls, the putamen-to-cerebellum and caudate-to-cerebellum ratios for [11C]beta-CFT were higher than those for [11C]beta-CIT (putamen: 3.15 +/- 0.39 for [11C]beta-CFT, and 1.84 +/- 0.10 for [11C]beta-CIT; caudate: 3.15 +/- 0.31 for [11C]beta-CFT, and 1.95 +/- 0.17 for [11C]beta-CIT). Reduction from mean control value in PD patients was greater for [11C]beta-CFT (45% in the putamen contralateral to the predominant symptoms, P < 0.001) than for [11C]beta-CIT (20%, P > 0.05). [11C]beta-CFT uptake in the caudate nucleus was also diminished in PD patients (to 80% of the control mean, P < 0.05), whereas [11C]beta-CIT was within normal range (reduced to 90% of the control mean). These results indicate that both [11C]beta-CIT and [11C]beta-CFT are useful PET ligands to study brain monoamine transporter in healthy controls and in patients with PD. However, [11C]beta-CFT seems superior to [11C]beta-CIT in this respect.
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PMID:PET examination of the monoamine transporter with [11C]beta-CIT and [11C]beta-CFT in early Parkinson's disease. 858 80

Neurological disorders in rat model of hemi-Parkinson's disease can be compensated by the transplantation of fetal nigral cells. However, the role of the dopamine transporter (DAT) in this recovery has not been clarified. To clarify this mechanism, we examined the expression of DAT in the caudate putamen (CPu) by in situ hybridization histochemistry (mRNA) and autoradiography (using the ligand [125I] beta-CIT, which labels DAT) and compared them with the recovery of motor disturbance revealed with methamphetamine-induced rotation. Models were made with the stereotaxic injection of 6-hydroxydopamine into the left side of the substantia nigra pars compacta. Cell suspensions from rat fetus (embryonic day 14-15) were transplanted into the lesioned side of CPu. Methamphetamine-induced rotation, expression of DAT mRNA, and [125I] beta-CIT binding were evaluated 2, 4 and 12 weeks after the transplantation. Methamphetamine-induced rotation recovered partly in the 2nd week and significantly in the 4th week. [125I] beta-CIT binding increased with time and the dense binding was detected 4 and 12 weeks after the transplantation. In all transplanted rats, cells expressing DAT mRNA were found in CPu. These results indicated that transplanted fetal dopaminergic cells maturated in CPu of host animals and extended nerve terminals where high density of DAT binding sites were found.
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PMID:Expression of dopamine transporter mRNA and its binding site in fetal nigral cells transplanted into the striatum of 6-OHDA lesioned rat. 880 21

The main neuropathological feature in Parkinson's disease (PD) is a severe degeneration of the dopaminergic neurons in the substantia nigra resulting in a loss of dopamine in the striatum. Recently, a new radioligand (beta-CIT) for single photon emission computed tomography (SPECT) became available for in vivo imaging of the dopamine transporter on nerve endings of dopaminergic neurons in the striatum. The present results demonstrate that [123I]-beta-CIT SPECT allows a discrimination between early and late PD patients. In our opinion, these preliminary data suggest that [123I]-beta-CIT SPECT should be used from now on in longitudinal studies (such as the DATATOP study) in which the effects of (putative) neuroprotective interventions in PD are monitored.
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PMID:Evaluation of [123I] beta-CIT binding with SPECT in controls, early and late Parkinson's disease. 899 76

In the development of novel Tc-99m-labeled tropane derivatives as dopamine transporter (reuptake site)-imaging agents, a series of neutral and lipophilic complexes containing bis-(aminoethanethiol) as a neutral complexing moiety for a [99mTc]TcO3+ center core was successfully prepared. Biological evaluation of the Tc-99m-labeled complexes 13-16 as central nervous system (CNS) dopamine transporter-imaging agents was reported. Synthesis of the tropane derivatives was achieved by stepwise reactions adding two aminoethanethiol units. The final free thiol ligands were obtained by deblocking the 4-methoxybenzyl protecting group with Hg(OAc)2 to obtain trifluoroacetate salts. All of the Tc-99m complexes, with the exception of 16, displayed good initial brain uptake and selective uptake in the striatal area, where dopamine transporters are concentrated. One of the compounds, [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo [3.2.1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethy] amino]ethanethiolato-(3-)-N2,N2',S2,S2'] oxo-[1R-(exo-exo)]- [99mTc]technetium,[99mTc]TRODAT-1 (13), displayed the highest initial uptake in rat brain (0.4% at 2 min post iv injection); the striatal/cerebellar (ST/ CB) ratio reached 2.8 at 60 min after an iv injection. The specific uptake in rat brain can be blocked by pretreating rats with a competing dopamine transporter binding agent, beta-CIT (RTI-55, 2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane; iv, 1 mg/kg), which reduced the regional brain uptake ratio (ST/CB) to 1.2. In contrast, the specific striatal uptake was not affected by pretreating rats with a noncompeting ligand, haldol (iv, 1 mg/kg). After an iv injection of 9 mCi of [99mTc]TRODAT-1 (13), in vivo images of baboon brain using single-photon emission-computed tomography exhibited excellent localization in striatum (basal ganglia), where dopamine neurons are known to be concentrated. This series of compounds may provide a convenient source of short-lived imaging agents for routine diagnosis of CNS diseases (i.e., Parkinson's disease) in which changes in the dopamine transporter concentration are implicated.
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PMID:Synthesis and characterization of technetium-99m-labeled tropanes as dopamine transporter-imaging agents. 901 23


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