123I-Ioflupane/SPECT binding to striatal dopamine transporter (DAT) uptake in patients with Parkinson’s disease, multiple system atrophy, and progressive supranuclear palsy

Abstract. We used SPECT and the tracer ¹²³I-Ioflupane to measure dopamine transporter (DAT) binding in the caudate nucleus and the putamen of 70 patients with Parkinsons disease (PD), 10 with multiple system atrophy (MSA-P type), and 10 with progressive supranuclear palsy (PSP). Data were compared with 12 age-matched control subjects. We found significant reductions in mean striatal values in all three forms of parkinsonism. However, decrements were significantly greater in PSP (0.51±0.39, p<0.01) compared with MSA-P (0.70±0.33) and PD (0.95±0.38). No differences were found between MSA and PD. Putamen/caudate ratios were greater in PSP (0.83±0.12, p<0.01) than in PD (0.51±0.11), suggesting a more-uniform involvement of dopamine nerve terminals in both caudate nucleus and putamen. Our results confirm that DAT binding can provide an accurate and highly sensitive measure of dopamine degeneration. PSP patients may show a different pattern of neuronal loss compared with MSA and PD.     

PET imaging of the dopamine transporter in progressive supranuclear palsy and Parkinson's disease

OBJECTIVE: To differentiate the patterns of dopamine transporter loss between idiopathic PD and progressive supranuclear palsy (PSP). METHODS: We used the radiotracer [11C]-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 = 0.0008) and the control group (p < 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.     

SPECT imaging of pre- and postsynaptic dopaminergic alterations in L-dopa-untreated PD

BACKGROUND: In PD, presynaptic dopamine transporters are known to be decreased, whereas postsynaptic striatal D2 receptors are proposed to be upregulated. However, the relationship between these alterations is not clear. OBJECTIVE: To evaluate the ability of SPECT to detect both the pre- and postsynaptic dopaminergic alterations of the striatum in patients with L-dopa-untreated PD. METHODS: We studied 10 L-dopa-untreated patients with clinically mild PD and 21 age-matched normal controls. Individuals had both presynaptic [123I]beta-CIT dopamine transporter and postsynaptic [123I]IBF D2 SPECT studies 1 week apart. RESULTS: In PD patients, the dopamine transporter binding potential Rv ipsilateral/contralateral to the most affected limbs was 30%/41%, 41%/50%, and 59%/68% lower than controls for caudate, anterior putamen, and posterior putamen, respectively. These bilateral Rv decreases showed a lateralized difference more reduced in the contralateral striatum as well as intrastriatal differences most reduced in the posterior putamen. In contrast, in PD patients the D2 binding potential Rv ipsilateral/contralateral was 15%/16% higher for caudate, 18%/14% higher for anterior putamen, and 28%/31% higher for posterior putamen. These bilateral Rv increases showed no lateralized differences and less marked intrastriatal differences. The motor Unified Parkinson's Disease Rating Scale scores negatively correlated with dopamine transporter Rv but not with D2 Rv. CONCLUSIONS: SPECT imaging can detect characteristic dopaminergic alterations in the striatum of dopa-untreated PD patients including the upregulation of postsynaptic D2 receptors (denervation supersensitivity). SPECT is widely available and is a promising clinical tool to evaluate PD patients.     

Dopamine Receptors in Parkinson's Disease: A Meta-Analysis of Imaging Studies

Dopamine receptors are abundant along the central nigrostriatal tract and are expressed as 5 subtypes in two receptor families. In PD, compensatory changes in dopamine receptors emerge as a consequence of the loss of dopamine nerve terminals or dopaminergic pharmacotherapy. We performed a systematic review and meta-analysis of the available PET and single-photon emission computed tomography studies that have investigated dopamine receptors in PD, PSP and MSA. The inclusion criteria were studies including human PET or single-photon emission computed tomography imaging; dopamine receptor tracers (D1-like or D2-like) and idiopathic PD, PSP, or MSA patients compared with healthy controls. The 67 included D2-like studies had 1925 patients. Data were insufficient for an analysis of D1-like studies. PD patients had higher striatal binding early in the disease, but after a disease duration of 4.36 years, PD patients had lower binding values than healthy controls. Striatal D2R binding was highest in unmedicated early PD patients and in the striatum contralateral to the predominant motor symptoms. PSP and MSA-P patients had lower striatal D2R binding than PD patients (14.2% and 21.8%, respectively). There is initial upregulation of striatal D2Rs in PD, which downregulate on average 4 years after motor symptom onset, possibly because of agonist-induced effects. The consistent upregulation of D2Rs in the PD striatum contralateral to the predominant motor symptoms indicates that receptor changes are driven by neurodegeneration and loss of striatal neuropil. Both PSP and MSA patients have clearly lower striatal D2R binding values than PD patients, which offers an opportunity for differential diagnostics. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society     

~(11)C-CFT PET显像评价帕金森病与多系统萎缩P型患者脑内多巴胺转运体分布特点的研究

目的基于~(11)C-CFT正电子发射计算机断层(PET)显像评价帕金森病(PD)与多系统萎缩P型(MSA-P)患者脑内多巴胺转运体(DAT)分布特点,评估~(11)C-CFT PET显像在PD与MSA-P鉴别诊断中的价值。方法回顾性分析年龄、性别和疾病严重程度匹配的32例MSA-P患者(MSA-P组)和56例PD患者(PD组)的临床资料以及~(11)C-CFT PET影像资料;另选择年龄匹配的健康对照者20例为对照组。应用感兴趣区技术获得3组研究对象的尾状核、前壳核和后壳核的DAT分布半定量值,对各感兴趣区的DAT分布半定量值、相互比值和不对称性进行对比研究。建立受试者工作特征曲线(ROL),利用曲线下面积评估基于~(11)C-CFT PET显像所得相关参数对PD和MSA-P的鉴别能力。结果与PD组比较,MSA-P组患者病程更短、进展速度更快(P0.000 1)。与对照组比较,PD组和MSA-P组尾状核、前壳核和后壳核的DAT分布半定量值均显著减低(P0.000 1),且后壳核降低最为显著。PD组和MSA-P组尾状核、前壳核和后壳核的DAT分布半定量值及其不对称指数比较均差异无显著性。PD组和MSA-P组纹状体各感兴趣区DAT分布半定量值中,前壳核/尾状核比值(AP/C)、后壳核/前壳核比值(PP/AP)均差异无显著性;但MSA-P组后壳核/尾状核比值(PP/C)PD组(P0.05),两组PP/C比值的ROL曲线下面积为0.696(P=0.002);以0.611作为PP/C比值的临界值,其对MSA-P和PD鉴别诊断的灵敏度和特异度分别为71.9%和62.5%。结论 ~(11)C-CFT PET显像可以精准显示MSA-P及PD患者脑内多巴胺能神经元的突触前功能损害,但尚不能有效鉴别两种疾病。     

The status of dopamine nerve terminals in Parkinson's disease and essential tremor: a PET study with the tracer [11-C]FE-CIT

Neuroimaging studies of the striatal dopamine transporter (DAT) are useful in the assessment of the dopaminergic system in Parkinson's disease (PD). We used positron emisson tomography (PET) and the tracer [11-C]FE-CIT to measure DAT binding in the caudate nucleus and putamen of 31 patients with PD, 5 with essential tremor and 8 healthy control subjects. Of the patients with PD, 17 were drug naive, while the others were either on levodopa or dopamine agonist monotherapy. DAT binding was significantly reduced in the caudate nucleus and to a greater extent in the putamen of PD patients compared to both healthy controls and essential tremor individuals. No overlap was observed between putamen values in PD and normals. No differences were found between controls and essential tremor subjects. These data confirm that measurements of DAT binding can provide an accurate and highly sensitive measure of degeneration in the dopamine system in PD.     

Brain dopamine-stimulated adenylyl cyclase activity in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy

The dopamine D(1) receptor is considered to participate in levodopa's antiparkinsonian action and levodopa-induced dyskinesias. We examined the functional status of the D(1) receptor in brain of patients with Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). Dopamine-stimulated adenylyl cyclase activity was significantly increased in putamen (+43%) and frontal cortex (+52%) in PD, normal in PSP, but decreased by 47% in putamen in MSA. The supersensitive dopamine D(1) receptors in both striatum and cerebral cortex in PD might compensate for dopamine deficiency, but could also contribute to long-term complications of levodopa therapy.     

123I]beta-CIT SPECT demonstrates decreased brain dopamine and serotonin transporter levels in untreated parkinsonian patients.

Striatal dopamine transporters (DATs) and serotonin transporters (SERTs) were evaluated in untreated patients with Parkinson's disease (PD) and controls using single-photon emission computed tomography (SPECT) with 2beta-carboxymethoxy-3beta-(4-iodophenyl)tropane ([123I]beta-CIT). The striatal DAT specific to non-displaceable uptake ratios of 29, and the SERT uptake measurements of 27, PD patients were compared with those of 21 and 16 controls, respectively. The results were correlated with Unified Parkinson's Disease Rating Scale (UPDRS) scores, the Hoehn & Yahr stage, age, duration of the disease, and the major PD signs. The specific DAT binding in the caudate, the putamen and the caudate/putamen ratio were measured. In all of the PD patients the striatal uptake values were bilaterally reduced, being 36.9% (P < 0.001) lower than those of the controls. In the hemiparkinsonian patients the reduction was greater on the side contralateral to the initial symptoms (33.3% vs. 27.8%) and the uptake ratios indicated a more pronounced deficit in the putamen (39.1%) than in the caudate (27.9%). The DAT uptake correlated with the UPDRS total score and activities of daily living (ADL) and motor subscores, the Hoehn & Yahr stage, and rigidity score. PD patients had significantly higher caudate to putamen ratios than the controls. In the PD patients the SERT values were lower in the thalamic and frontal regions. The SERT uptake ratio of the frontal area correlated with the UPDRS subscore I. [123I]beta-CIT SPECT provides a useful method for confirming the clinical diagnosis of PD with correlation to disease severity. Additionally, this technique allows the simultaneous measurement of SERT uptake and shows that PD patients, interestingly, seem to have decreased SERT availability in the thalamic and frontal areas.     

Altropane,a SPECT or PET imaging probe for dopamine neurons: III. Human dopamine transporter in postmortem normal and Parkinson's diseased brain

Increasing evidence suggests that the dopamine transporter is situated almost exclusively on dopamine neurons. Accordingly, it is an valuable marker for Parkinson's disease and other pathological states of dopamine neurons. We previously demonstrated that the potent dopamine transport inhibitor [¹²⁵I]altropane (IACFT:E-N-iodoallyl-2β-carbomethoxy-3β-(4-fluorophenyl)tropane) is a high affinity selective probe for the dopamine transporter in monkey brain and an effective SPECT imaging agent in nonhuman primate brain. We now report the binding properties of [¹²⁵I]altropane in postmortem tissue of normal human brain and compare the findings to Parkinson's diseased brain. In homogenates of human brain putamen, [¹²⁵I]altropane bound with high affinity (K_D: 4.96 ± 0.38 nM, n = 4) and site density (B_MAX: 212 ± 41.1 pmol/g original wet tissue weight) well within the density range reported previously for the dopamine transporter in this brain region. Drugs inhibited [¹²⁵I]altropane binding with a rank order of potency that corresponded closely to their rank order for blocking dopamine transport (r 0.98, P < 0.001). In postmortem Parkinson's diseased brain, bound [¹²⁵I]altropane (1 nM) was markedly reduced (89%, 99% in putamen, depending on measures of nonspecific binding) compared with normal aged-matched controls (normal putamen: 49.2 ± 8.1 pmol/g; Parkinson's diseased putamen: 0.48 ± 0.33 pmol/g; n = 4). In vitro autoradiography, conducted in tissue sections at a single plane of the basal ganglia, revealed high levels of [¹²⁵I]altropane binding the caudate nucleus and putamen, but lower levels (73% of the caudate-putamen) in the nucleus accumbens (n = 7). In Parkinson's diseased brains (n = 4), [¹²⁵I]altropane binding was 13% of the levels detected in normal putamen, 17% of normal values in the caudate nucleus, and 25% of normal levels in nucleus accumbens. The association of [¹²⁵I]altropane to the dopamine transporter in human postmortem tissue, the marked reduction of [¹²⁵I]altropane binding in Parkinson's diseased brains, its rapid entry into brain and highly localized distribution in dopamine-rich brain regions, support its use as a probe for monitoring the dopamine transporter in vitro and in vivo by SPECT imaging. Synapse 29:116–127, 1998. © 1998 Wiley-Liss, Inc.     

Imaging essential tremor

To investigate over time changes in striatal dopamine transporter (DAT), we performed two sequential N‐ω‐fluoropropyl‐2β‐carbomethoxy‐3β‐(4‐iodophenyl) tropane single photon computed tomography (SPECT) scans in 20 subjects with essential tremor (ET), in 13 with Parkinson disease (PD) and in 23 healthy controls (HC, one scan only). We also performed an [^99mTc]ethyl cysteinate dimer bicisate SPECT exam for regional brain network analysis in 9 ET, in a second group of 18 PD (9 with tremor, tPD and 9 akinetic‐rigid dominant, arPD) and in 8 HC. PD subjects had a reduced DAT binding in comparison to ET and HC with an annual decline rate of 7.3% in the contralateral putamen. There were no mean uptake differences between ET and HC at baseline and no uptake loss over time in ET. A discriminant analysis grouped 30% (first scan) and 5% (second scan) of ET as PD and a partition analysis showed overlap between ET and PD for caudate nucleus uptake. Spatial covariance analysis revealed that the expression of the PD‐related regional pattern separated both tPD and arPD from ET and HC. In conclusion, PD and ET do not share a common pattern of dopaminergic loss over time. However, mild impairment of dopamine transporter in the caudate nucleus may contribute to tremor onset in ET. © 2010 Movement Disorder Society     

Presynaptic and postsynaptic striatal dopaminergic function in neuroacanthocytosis: a positron emission tomographic study

Using [18F]dopa, [11C]raclopride, C15O2, and positron emission tomography, we have assessed striatal dopamine storage capacity, dopamine D2-receptor integrity, and regional cerebral blood flow, respectively, of 6 patients with neuroacanthocytosis. The patients with neurocanthocytosis all had chorea and variable combinations of seizures, dementia, axonal neuropathy, and orolingual self-multiation. [18F]dopa positron emmission tomographic findings were compared with 30 normal controls and 16 patients with sporadic, L-dopa-responsive, Parkinson's disease. Caudate and anterior putamen [18F]dopa uptake were normal in patients with neuroacanthocytosis, but mean posterior putamen [18F]dopa uptake was reduced to 42% of normal, similar to that in patients with Parkinson's disease. In patients with neuroacanthocytosis, mean equilibrium caudate: cerebellum and putamen: cerebellum [11C]raclopride uptake ratios were reduced to 54% and 62% of normal, compatible with a 65% and 53% loss of caudate and putamen D2-receptor-binding sites, respectively. Striatal and frontal blood flow was also depressed. The severe loss of D2-receptor-bearing striatal neuron, with concomitant loss of dopaminergic projections from the nigra to the posterior putamen, is consistent with both chorea and extrapyramidal rigidity being features of patients with neuroacanthocytosis.     

Parametric mapping of [18F]FPCIT binding in early stage Parkinson's disease: a PET study

We have shown that fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane ([(18)F]FPCIT) and PET offer a valuable means of quantifying regional abnormality in dopamine transporter (DAT) imaging associated with Parkinson's disease (PD). The objective of this study was to delineate the topographic distribution of DAT binding in early stage idiopathic PD using statistical parametric analysis of [(18)F]FPCIT PET data. We performed dynamic PET studies in 15 hemi-parkinsonian (Hoehn & Yahr I) patients and 10 age-matched normal volunteers over 100 min and calculated images of [(18)F]FPCIT binding ratios on a pixel-by-pixel basis. Statistical parametric mapping (SPM) was then used to localize binding reductions in PD and to compute the absolute change relative to normal. [(18)F]FPCIT binding decreased significantly in the contralateral posterior putamen of the PD group (P < 0.001, corrected). A significant reduction was also seen in the ipsilateral putamen, which was smaller in extent but localized more posteriorly. A quantitative comparison of DAT binding in the two clusters showed that the onset of motor symptoms in PD was associated with an approximate 70% loss relative to the normal mean in the contralateral posterior putamen. These results suggest that SPM analysis of [(18)F]FPCIT PET data can be used to quantify and map abnormalities in DAT activity within the human striatum. This method provides a useful tool to track the onset and progression of PD at its earliest stages.     

Reduced striatal [123 I]FP-CIT binding in SCA2 patients without parkinsonism

Degeneration of substantia nigra has been described in spinocerebellar ataxia type 2 (SCA2). In this study, dopamine transporter (DAT) density with [123 I]FP-CIT SPECT was studied in six SCA2 patients with no parkinsonian signs, six Parkinson's disease (PD) patients, and six controls. Marked striatal DAT loss was found in both SCA2 and PD patients. However, a more severe reduction in the caudate and a higher putamen to caudate ratio distinguished SCA2 from PD patients, suggesting a more uniform nigrostriatal impairment in SCA2. Striatal DAT density of SCA2 patients correlated with the severity of cerebellar ataxia.     

The influence of genetic variants on striatal dopamine transporter and D2 receptor binding after TBI

Dopamine (DA) neurotransmission influences cognition and recovery after traumatic brain injury (TBI). We explored whether functional genetic variants affecting the DA transporter (DAT) and D2 receptor (DRD2) impacted in vivo dopaminergic binding with positron emission tomography (PET) using [¹¹C]βCFT and [¹¹C]raclopride. We examined subjects with moderate/severe TBI (N=12) ∼1 year post injury and similarly matched healthy controls (N=13). The variable number of tandem repeat polymorphism within the DAT gene and the TaqI restriction fragment length polymorphism near the DRD2 gene were assessed. TBI subjects had age-adjusted DAT-binding reductions in the caudate, putamen, and ventral striatum, and modestly increased D2 binding in ventral striatum versus controls. Despite small sample sizes, multivariate analysis showed lower caudate and putamen DAT binding among DAT 9-allele carriers and DRD2 A2/A2 homozygotes with TBI versus controls with the same genotype. Among TBI subjects, 9-allele carriers had lower caudate and putamen binding than 10/10 homozygotes. This PET study suggests a hypodopaminergic environment and altered DRD2 autoreceptor DAT interactions that may influence DA transmission after TBI. Future work will relate these findings to cognitive performance; future studies are required to determine how DRD2/DAT1 genotype and DA-ligand binding are associated with neurostimulant response and TBI recovery.     

Serotonergic markers in Parkinson's disease and levodopa‐induced dyskinesias

Preclinical animal models implicate serotonin neurons in the pathophysiology of levodopa (l ‐dopa)–induced dyskinesias in Parkinson's disease (PD), but effective treatment remains elusive. We examined the relationship between serotonin and l ‐dopa–induced dyskinesias in a pathologically confirmed cohort of PD patients. We obtained brain tissue from 44 PD cases and 17 age‐matched controls and assessed monoamine levels and the serotonin and dopamine transporters in the striatum, and the extent of dopaminergic and serotonergic cell preservation in the substantia nigra (SN) and the dorsal raphe nuclei (DRN), respectively. As expected, PD patients demonstrated a severe loss of all dopaminergic markers, including dopamine (P < 0.0001) and the dopamine transporter (P < 0.0001) in the striatum, and dopaminergic neurons (P < 0.001) in the SN, compared with controls. Marked serotonin loss was observed in the caudate (but not putamen) in PD patients compared with controls (P < 0.001), but no difference was found in the levels of the serotonin transporter in the striatum or density of serotonergic neurons in the DRN between these groups, suggesting a functional but not structural change in the serotonergic system in PD. No difference was seen in levels of serotonergic and dopaminergic markers in the striatum between PD patients with and without dyskinesias, or between cases separated according to the clinical severity of their dyskinesias. The absence of a correlation between striatal serotonin markers and the incidence and severity of l ‐dopa–induced dyskinesias suggests that an intact and functioning serotonergic system is not a risk factor for developing dyskinesias in PD. © 2015 International Parkinson and Movement Disorder Society     

Influence of L-dopa and pramipexole on striatal dopamine transporter in early PD

BACKGROUND: Animal data indicate that chronic exposure to dopaminergic drugs can alter levels of the dopamine transporter (DAT), which is critically involved in regulation of synaptic dopamine levels. DAT changes could influence the response to therapy in PD. METHODS: A randomized, assessor-blinded, placebo-controlled clinical trial was performed in subjects with early PD to determine whether L-dopa or pramipexole might regulate striatal DAT binding as measured by PET with [(11)C]RTI-32. Thirty clinically asymmetrical patients were randomly assigned to receive 6 weeks of L-dopa (300/75 mg/d), pramipexole (1.5 mg/d), or placebo; PET studies were performed before and after treatment. RESULTS: Mean interval change in DAT binding was significantly reduced by 16% to 22% in all striatal regions (caudate, anterior and posterior putamen) of the L-dopa-treated patients, whereas significant changes in the pramipexole-treated patients were limited to the contralateral caudate (-15%), ipsilateral anterior putamen (-14%), and posterior putamen (-20%). In the placebo group there were significant changes in contralateral caudate (-11%) and ipsilateral anterior putamen (-12%). L-dopa and pramipexole produced similar clinical benefit. CONCLUSIONS: Short-term therapy with L-dopa and, to a lesser extent, pramipexole can modestly down-regulate striatal DAT in patients with early PD. Decreased striatal DAT could increase dopaminergic neurotransmission with potential benefit, but might also play a role in the development of dopamine-related response fluctuations in patients with advanced disease. Our data also suggest caution in interpretation of longitudinal imaging studies employing DAT to assess disease progression and the efficacy of neuroprotective agents.     

The pattern of FP-CIT PET in pure white matter hyperintensities–related vascular parkinsonism

ObjectivesTo determine whether vascular parkinsonism (VaP) patients with visually normal dopamine transporter (DAT) scans have presynaptic dopaminergic depletion.MethodsWe enrolled 23 VaP patients who had parkinsonism, relevant diffuse subcortical white matter hyperintensities (WMH), and visually normal DAT scans, 23 Parkinson's disease (PD) patients, and 31 control subjects. By quantitatively analyzing ¹⁸F–N-(3-fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane (¹⁸F-FP-CIT) positron emission tomography, we compared the pattern of striatal DAT availability among groups. The discriminatory power of striatal DAT availability to differentiate VaP patients from control subjects or PD patients was assessed using receiver operating characteristics (ROC) analyses. Additionally, correlation analysis was performed to determine whether WMH severity or Unified Parkinson Disease Rating Scale Part III (UPDRS-III) score is related to presynaptic dopaminergic depletion in VaP.ResultsVaP patients exhibited decreased DAT availability in all striatal subregions, including posterior putamen, compared to control subjects. VaP patients and control subjects had similar patterns of anteroposterior and ventrodorsal DAT gradients in caudate and putamen level, but VaP patients exhibited significantly different patterns at putamen level, relative to PD patients. The severity of periventricular WMH was significantly correlated with all substriatal DAT availability in VaP, but not with UPDRS-III scores. The ROC analysis showed that DAT availability in caudate and posterior putamen had a fair discriminatory power when differentiating VaP patients from control subjects.ConclusionsThis study demonstrates that VaP patients with WMH exhibited diffusely decreased DAT availability without any specific regional gradients of DAT patterns distinct from either control subjects or PD patients.     

Imaging in Parkinson's disease: the role of monoamines in behavior.

Positron emission tomography (PET) and single photon emission computed tomography (SPECT) can measure striatal dopamine (DA) terminal function in vivo as reflected by DA storage capacity and transporter binding. In Parkinson's disease (PD) posterior dorsal putamen DA terminals are initially targeted, the anterior putamen and head of caudate subsequently becoming affected. In contrast, dopaminergic function in pallidal, amygdala, and cingulate regions is upregulated in early PD and only later becomes reduced. Rigidity and bradykinesia in PD have been shown to correlate with loss of putamen dopaminergic function, whereas performance on executive and working memory tasks correlates with integrity of caudate dopaminergic terminals. 11C-RTI32 PET, a marker of noradrenergic and dopaminergic transporter binding, can be used to assess noradrenergic along with dopaminergic terminal function. Serotonergic transporter binding can be assessed with 11C-DASB PET and 123I-beta CIT SPECT, whereas HT1A binding can be measured with 11C-WAY100635 PET. With these modalities, the relationship between mood, noradrenergic and serotonergic function can be examined in PD. The functional effects of focal DA replacement on DA storage capacity and patterns of brain activation via implantation of fetal midbrain cells or glial derived neurotrophic factor (GDNF) infusion into putamen of PD patients has been examined with PET. Both approaches lead to consistently increased levels of putamen 18F-dopa uptake, and cell implantation can restore levels of frontal activation. Clinical outcome, however, has proved to be variable and off-medication dyskinesias are an unwanted side effect in transplanted cases. Dopamine release after pharmacological challenges or during behavioral tasks can be assessed indirectly by studying changes in receptor availability to PET radioligands. Stereotyped sequential movements are associated with striatal DA release, and this increases with more complex behaviors and the presence of financial incentives, which also increase frontal DA levels. Parkinson patients release less putamen DA than healthy control subjects during stereotyped finger movements. Interestingly, those PD patients who develop a dopa dependency syndrome, craving their medication, generate significantly greater levels of ventral striatal DA compared with similarly disabled patients without such a psychological dependency. In the future, functional imaging is likely to throw light on the roles of peptide transmission in regulating mood and behavior as non-peptide analogue ligands become available. Novel markers of amyloid plaque load will also help clarify the etiology of dementia in PD.     

The interaction between dopamine transporter function,gender differences,and possible laterality in depression

The Dopamine Transporter (DAT) can reflect the general state of striatal dopamine activity. This current study examined the role of DAT in depressed patients before and after bupropion treatment. Twenty-three patients with major depression were treated with bupropion for 8 weeks. Before and after the treatment, they and 20 normal subjects received the radioligand ^99mTc-TRODAT-1 single photon emission tomography scan (SPECT). Subjects were assessed with the Hamilton Depression Rating Scale. All DAT images were spatially normalized to an averaged brain template, and the specific binding ratios of the striatum, caudate, and putamen were calculated according the formulae of: [region counts] / [occipital counts] - 1. Depressed patients had greater DAT availability on both sides of the striatum. DAT binding was significantly decreased in the striatum after bupropion treatment. Women had higher initial and final DAT binding in the right and left caudate when compared to depressed men. DAT binding decreased in all areas of the brain in women after successful antidepressant treatment, but only in the right caudate of men. Depressed patients had a greater availability of DAT; it was decreased after bupropion treatment.Women seemed to have more DAT availability.     

Dopamine transporter binding in Gilles de la Tourette syndrome: a [123I]FP-CIT/SPECT study

Objective: To investigate dopamine transporter binding in Gilles de la Tourette syndrome (GTS) with SPECT and [¹²³I]FP‐CIT. Method: Ten neuroleptic naïve/free patients with GTS, and 10 age‐ and gender‐matched normal volunteers were studied. Subjects were clinically evaluated. GTS severity and affective symptoms were measured and the presence of GTS‐related behaviours were recorded. Results: The GTS group showed significantly higher binding in both caudate and putamen nuclei than the controls. No associations were found between striatal binding ratios and measures of affect or GTS‐related behaviours. Conclusion: Patients with GTS show higher striatal binding of FP‐CIT to the striatum in comparison with age‐ and gender‐matched control subjects, indicating that dopamine transporter abnormalities are involved in the pathophysiology of GTS. These abnormalities appear to be distributed across both caudate and putamen.