Diffusion-weighted magnetic resonance imaging differentiates Parkinsonian variant of multiple-system atrophy from progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) and the parkinsonian variant of multiple-system atrophy (MSA-P) may present with a similar phenotype. Magnetic resonance diffusion-weighted imaging (DWI) has been shown to be a sensitive discriminator of MSA-P from Parkinson's disease (PD). We studied 20 PSP, 11 MSA-P, 12 PD patients and 7 healthy controls in order to investigate whether regional apparent diffusion coefficients (rADCs) help distinguish PSP and MSA-P; whether rADCs are correlated with clinical disease severity scores; and the relationship between brainstem and cerebellar volumes and rADCs in PSP and MSA-P. The Unified Parkinson's Disease Rating Scale, Hoehn and Yahr score, Mini Mental State Examination, and frontal assessment battery were recorded in all patients. Regional ADCs were measured in the middle cerebellar peduncle (MCP), caudal and rostral pons, midbrain, decussating fibers of the superior cerebellar peduncle, thalamus, putamen, globus pallidus, caudate nucleus, corpus callosum, frontal and parietal white matter, as well as the centrum semiovale. In MSA-P, rADCs in the MCP and rostral pons were significantly greater than in PSP (P < 0.001 and 0.009) and PD (P < 0.001 and = 0.002). Stepwise logistic regression revealed that the MCP rADC distinguishes MSA-P from PSP with a sensitivity of 91% and a specificity of 84%. Increased brainstem rADCs were associated with motor deficit in MSA-P and PSP. Increased rADCs in the pons and MCP were associated with smaller pontine and cerebellar volumes in MSA-P. rADCs distinguish MSA-P from PSP. These have a clinical correlate and are associated with reduced brainstem and cerebellar volumes.     

Diffusion-weighted MRI differentiates the Parkinson variant of multiple system atrophy from PD

OBJECTIVE AND BACKGROUND: Routine MRI as well as MR volumetry and MRS have been shown to contribute to the differential diagnosis of the Parkinson variant of multiple system atrophy (MSA-P) and PD. However, it is currently unknown whether diffusion-weighted imaging (DWI) discriminates these disorders. METHODS: Ten patients with MSA-P (mean age, 64 years) were studied, 11 with PD (mean age, 64 years), and seven healthy volunteers (mean age, 59 years) matched for age and disease duration. Regional apparent diffusion coefficients (rADC) were determined in different brain regions including basal ganglia, gray matter, white matter, substantia nigra, and pons. RESULTS: Patients with MSA-P had higher putaminal rADC (median 0.791 x 10(3)/mm(2)/s) than both patients with PD (median 0.698 x 10(3)/mm(2)/s, p < 0.001) and healthy volunteers (median 0.727 x 10(3)/mm(2)/s, p < 0.001). There were no significant differences in putaminal rADC between patients with PD and healthy volunteers. Moreover, none of the putaminal rADC values in the PD and control group surpassed the lowest value in the MSA-P group. There were no significant group differences in the rADC values in other brain regions such as pons, substantia nigra, globus pallidus, caudate nucleus, thalamus, or gray and white matter. Putaminal rADC values correlated significantly with Unified PD Rating Scale OFF scores in patients with MSA as measured by the Spearman rank test. CONCLUSION: DWI, even if measured in the slice direction only, is able to discriminate MSA-P and both patients with PD and healthy volunteers on the basis of putaminal rADC values. The increased putaminal rADC values in Parkinson variant of multiple system atrophy are likely to reflect ongoing striatal degeneration, whereas most neuropathologic studies reveal intact striatum in PD. Diffusion-weighted imaging may represent a useful diagnostic tool that can provide additional support for a diagnosis of Parkinson variant of multiple system atrophy.     

Dopamine D2 receptor binding is reduced in Wilson's disease: Correlation of neurological deficits with striatal123I-Iodobenzamide binding

Summary To visualise and quantify dopamine D2 receptor binding in the corpus striatum of patients with neurological Wilson's disease (WD) 123I-Iodobenzamide (IBZM) binding was measured using single photon emission computer tomography (SPECT). Ratios of striatal to frontal countrates were calculated in 8 patients and in 21 healthy control subjects. We found reduced IBZM binding ratios in all patients with WD in comparison to those in controls (1.48 +- 0.13 vs. 1.73 +- 0.09). The reduction in IBZM binding was correlated with the overall severity of neurological deficits and the severity of dysarthria (correlation coefficients –0.86 [p < 0.01] and –0.79 [p s< 0.01], respectively). When patients of three different subgroups of neurological WD were compared no differences in IBZM binding were found. We conclude that assessing basal ganglia function in vivo using IBZM-SPECT is a valuable diagnostic tool in WD.     

Striatal dopamine release after prefrontal repetitive transcranial magnetic stimulation in major depression: preliminary results of a dynamic [123I] IBZM SPECT study

Though there is considerable evidence that prefrontal repetitive transcranial magnetic stimulation (rTMS) exerts antidepressant effects, the neurobiological action of rTMS in patients with depression is poorly understood. Preclinical studies in animals and humans have demonstrated that prefrontal rTMS can induce dopamine release in mesostriatal and mesolimbic regions. We therefore investigated whether rTMS also modulates striatal dopaminergic neurotransmission in depressed patients using a dynamic [123I] iodobenzamide (IBZM) single photon emission computed tomography (SPECT) approach. Five patients with a major depressive episode (DSM-IV) underwent an acute 10 Hz rTMS challenge with 3000 stimuli over the left dorsolateral prefrontal cortex during an [123I] IBZM-SPECT bolus and constant infusion protocol. In four subjects the protocol was repeated after a three week rTMS standard treatment. Striatal IBZM binding to dopamine D2 receptors was assessed with a region-of-interest (ROI) technique. The change in striatal IBZM binding after the rTMS challenge was regarded as measure of change in endogenous striatal dopamine. Data of nine SPECT investigations showed a significant reduction by 9.6+/-6.2% in IBZM binding to striatal dopamine D2 receptors after rTMS challenge compared to baseline (p=0.01, Wilcoxon test). In this preliminary study, the reduction of IBZM binding observed after rTMS challenge is suggestive of a release in endogenous dopamine induced by prefrontal rTMS. In future, this approach can be used to differentiate specific and non-specific reward-related effects of rTMS on dopaminergic neurotransmission.     

Multiple system atrophy: natural history, MRI morphology, and dopamine receptor imaging with 123IBZM-SPECT.

Sixteen patients with a clinical diagnosis of probable multiple system atrophy (MSA) were examined clinically by MRI and by 123I-iodobenzamide single photon emission computed tomography (IBZM-SPECT). The clinical records of another 16 patients were also analysed retrospectively. On the basis of their clinical presentation, patients were subdivided into those with prominent parkinsonism (MSA-P, n = 11) and those with prominent cerebellar ataxia (MSA-C, n = 21). Autonomic symptoms were present in all patients and preceded the onset of motor symptoms in 63% of patients. Calculated median lifetime and the median time to become wheelchair bound after onset of disease were significantly shorter for MSA-P than for MSA-C (lifetime: 4.0 v 9.1 years; wheelchair: 3.1 vs 5.0 years) suggesting a better prognosis for cerebellar patients. A significant loss of striatal dopamine receptors (below 2 SD threshold) was detected by IBZM-SPECT in 63% of the patients (56% below 2.5 SD threshold). There was no difference between patients with MSA-C and those with MSA-P in the proportion with significant receptor loss and the extent of dopamine receptor loss. Planimetric MRI evaluation showed cerebellar and brainstem atrophy in both groups. Atrophy was more pronounced in patients with MSA-C than in those with MSA-P. Pontocerebellar hyperintensities and putaminal hypointensities on T2 weighted MRI were found in both groups. Pontocerebellar signal abnormalities were more pronounced in MSA-C than in MSA-P, whereas the rating scores for area but not for intensity of putaminal abnormalities were higher in MSA-P. MRI and IBZM-SPECT provide in vivo evidence for combined basal ganglia and pontocerebellar involvement in almost all patients in this series.     

Diffusion weighted imaging best discriminates PD from MSA-P: A comparison with tilt table testing and heart MIBG scintigraphy.

Both diffusion weighted magnetic resonance imaging (DWI) of the basal ganglia and meta-iodobenzylguanidin (MIBG) scintigraphy of the heart have been reported useful in the differential diagnosis of patients with Parkinson's disease (PD) vs. the parkinson variant of multiple system atrophy (MSA-P). Their diagnostic value, however, has never been directly compared in patients with parkinsonism and autonomic dysfunction. We have studied 9 patients with PD and 9 patients with MSA-P matched for age and disease severity. Regional trace of the diffusion tensor values were determined in the putamina. Cardiac MIBG uptake was quantified by comparing regions of interest over heart and mediastinum Heart/Mediastinum (H/M) ratio. Furthermore, all patients underwent tilt testing. PD patients showed significantly lower H/M ratios than normal controls; however, there was considerable overlap between the two patient groups. We did not detect any significant differences of blood pressure response to passive tilt between the two patient groups. Sensitivity of MIBG scintigraphy versus DWI for the differentiation of MSA-P from PD was 55.6% vs. 100%, specificity 88.8% vs. 100%, and area under the curve 0.802 vs. 1.000. Our data suggest that DWI is superior to both tilt table testing and MIBG scintigraphy in the differential diagnosis of PD versus MSA-P.     

Topography of putaminal degeneration in multiple system atrophy: a diffusion magnetic resonance study.

There is neuropathologic evidence that, in early stages of the Parkinson variant of multiple system atrophy (MSA-P), the putamen shows a distinct topographical pathology affecting predominantly the dorsolateral and caudal regions while leaving the rostral to midparts almost intact. We investigated the topographic profile of putaminal degeneration in MSA-P patients in vivo by means of diffusion-weighted imaging (DWI), which has been shown to reveal abnormalities in the basal ganglia of patients with MSA-P compared to patients with PD and healthy controls. For this purpose, regional trace of the diffusion tensor (rTrace(D)) values were determined in the entire, anterior, and posterior putamen in 15 patients with probable MSA-P, in 20 patients with PD, and in 11 healthy volunteers matched for age and disease duration. MSA-P patients had significantly higher rTrace(D) values in entire, anterior, and posterior putamen compared to both controls and PD patients. Trace(D) values were significantly higher in the posterior compared to the anterior putamen in the MSA-P group. There were no significant differences between posterior and anterior putamen in both the control and PD group. Our study demonstrates prominent involvement of the posterior putamen in early disease stages of MSA-P in vivo by assessing putaminal diffusivity with the help of DWI.     

Abnormalities of dopaminergic neurotransmission in SCA2: A combined 123I‐βCIT and 123I‐IBZM SPECT study

Extrapyramidal features may occur in spinocerebellar ataxias consistent with neuropathological evidence of nigrostriatal involvement. Recently, striatal dopaminergic neurotransmission was found to be abnormal in the uncommon parkinsonian presentation of spinocerebellar ataxia type 2 (SCA2). We have investigated, therefore, striatal dopamine transporter and D2 receptor function in a series of 9 patients with the more common ataxic presentation of SCA2 using single photon emission computed tomography and β‐CIT as well as IBZM. Age‐matched healthy subjects and patients with Parkinson's disease (PD) served as controls. All except 1 SCA2 patient exhibited slowness of limb movements without rigidity or rest tremor. In addition, cervical dystonia was present in 5 and dystonic head tremor in 2 SCA2 patients. Striatocerebellar (S/C) ratios of β‐CIT binding were significantly reduced in SCA2 patients compared to control subjects, and they were within the range of PD patients. S/C ratios of IBZM binding were significantly reduced in SCA2 patients compared to control subjects. We conclude that dopaminergic neurotransmission is impaired in the ataxic presentation of SCA2, with a prominent loss of striatal dopamine transporter function. Both slowness of limb movements as well as dystonia in the ataxic SCA2 phenotype may reflect dysfunction not only at cerebellar but also at basal ganglia level. © 2004 Movement Disorder Society     

Marked reduction of striatal dopamine D2 receptors as detected by 123IBZM-SPECT in a Wilson's disease patient with generalized dystonia.

[123I]iodobenzamide-single photon emission computed tomography (IBZM-SPECT) was employed to study the distribution of dopamine D2 receptors in a patient with biochemically proven Wilson's disease presenting with generalized dystonia. IBZM is a dopamine D2 receptor antagonist with high affinity and specific binding to basal ganglia detectable by SPECT. IBZM-SPECT in this patient (age, 20 years) displayed a striatum to frontal cortex ratio of 1.2 compared to 1.55 +/- 0.05 (mean +/- SD) in normal controls (n = 7; mean age, 53.3 years). In parallel with this finding, MRI with heavily T2-weighted sequences showed atrophy and low signal intensity changes of the basal ganglia. There was no improvement of dystonia after a subcutaneous injection of apomorphine. In contrast, IBZM-SPECT of a neurologically asymptomatic Wilson's disease patient (age, 21 years) displayed a striatum to frontal cortex ratio of 1.6. The MRI scan of this patient was normal. It is suggested that the observed apomorphine-unresponsive generalized dystonia in this Wilson's disease patient is related to striatal lesions proven by IBZM-SPECT and MRI.     

Striatal dopaminergic D(2) receptor density measured by [(123)I]iodobenzamide SPECT in the prediction of treatment outcome of alcohol-dependent patients

OBJECTIVE: The authors' goal was to study striatal dopaminergic dopamine 2 (D(2)) receptors as a biological marker of early relapse in detoxified alcoholic patients by using [(123)I]iodobenzamide ([123I]IBZM) single photon emission computed tomography (SPECT). METHOD: The authors performed [(123)I]IBZM SPECT on 21 alcohol-dependent inpatients during detoxification and on nine healthy volunteers, using the ratios of basal ganglia to occipital lobes for SPECT quantification. Depending on treatment outcome 3 months after hospital discharge, patients were determined to be relapsers or nonrelapsers. RESULTS: Alcohol-dependent subjects with early relapse (within 3 months after hospital discharge) showed a higher uptake of [(123)I]IBZM in the basal ganglia during detoxification (mean ratio=1.83, SD=0.9) than patients who did not have early relapse (mean ratio=1.69, SD=0.11). CONCLUSIONS: These results suggest that low levels of dopamine, or an increased density of free striatal dopaminergic D(2) receptors, could be related to early relapse in alcohol-dependent patients. Therefore, [(123)I]IBZM SPECT could become a biological marker of vulnerability to relapse for alcoholic patients in recovery.     

Steele-Richardson-Olszewski-Syndrome: the relation of dopamine D2 receptor binding and subcortical lesions in MRI

Summary. We compared ¹²³I-iodobenzamide single photon emission computed tomography (IBZM-SPECT) for imaging of striatal dopamine D₂ receptors in vivo, and MRI in 32 patients with the clinical diagnosis of progressive supranuclear palsy (PSP). We found a significant inter-dependence of reduction of specific striatal IBZM binding indicative of striatal degeneration and of the absence of multiple signal hyperintensities in MRI; age had no influence neither on IBZM binding nor on signal hyperintensities. We conclude that the presence of multiple signal hyperintensities should raise doubt on the correct clinical diagnosis. Received July, 2001; accepted October 31, 2001     

Decrease of D2 receptors indicated by 123I-iodobenzamide single-photon emission computed tomography relates to neurological deficit in treated Wilson's disease.

Single-photon emission computed tomography with 123I-iodobenzamide, a dopamine D2 receptor antagonist, was employed to study dopamine D2 receptor densities in 17 patients with biochemically proved Wilson's disease and stable neurological status with therapy and in 5 age-matched control subjects. Of the 17 patients with Wilson's disease, 5 were neurologically asymptomatic, 3 had cerebellar signs, 1 exhibited a mild parkinsonian syndrome, 7 showed a parkinsonian syndrome and cerebellar signs, and 1 had generalized dystonia and a parkinsonian syndrome. In 5 age-matched control subjects specific isotope binding as calculated by the basal ganglia to frontal cortex ratio was 1.57 +/- 0.04 (mean +/- standard deviation). The ratio in patients with Wilson's disease ranged from 1.56 +/- 0.05 (n = 5, asymptomatic patients) to 1.17 +/- 0.02 (n = 4, marked neurological impairment). We observed an almost linear correlation between the reduction of 123I-iodobenzamide (IBZM) binding and the severity of neurological signs at the time of IBZM-SPECT (correlation coefficient, -0.84; p < 0.01). We suggest that the reduction of postsynaptic striatal dopamine D2 receptors as detected by IBZM-SPECT reflects striatal neuronal damage in Wilson's disease.     

Noctural myoclonus syndrome (periodic movements in sleep) related to central dopamine D2-receptor alteration

The nocturnal myoclonus syndrome (NMS) consists of stereotyped, repetitive jerks of the lower limbs that occur during sleep or wakefulness. NMS is often related with restless-legs syndrome (RLS) and can cause severe sleep disturbances and daytime sleepiness. The efficacy of dopamine agonists in the treatment points to a dopaminergic dysfunction in NMS. We investigated the central dopamine D2-receptor occupancy with [¹²³I] labeled (S)-2-hydroxy-3-iodo-6-methoxy-([1-ethyl-2-pyrrolidinyl]methyl) benzamide (IBZM) (a highly selective CNS D2 dopamine receptor ligand) ([¹²³I]IBZM) and single photon emission tomography (SPET) in 20 patients with NMS and in 10 healthy controls. In most of the patients with NMS there was a lower [¹²³I]IBZM binding in the striatal structures compared to controls. The results indicate that NMS is related to a decrease of central D2-receptor occupancy.     

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     

Imaging of dopamine transporters with technetium-99m TRODAT-1 and single photon emission computed tomography.

The authors wanted to evaluate the usefulness of 99Tcm-TRODAT-1 as an imaging agent for measuring changes in dopamine transporter concentrations in Parkinson disease (PD) and correlate the findings to the severity of the disease as measured by the Hoehn and Yahr scale (H/Y). Twenty-two healthy volunteers and 27 patients with PD of H/Y stage I-IV were evaluated. Acquisitions were performed 2 hours after injection of 99Tcm-TRODAT-1. Regions of interest were drawn over the striatum and the cerebellum, and the ratios of striatum-to-cerebellum (ST/CB) were calculated. Patients with PD showed a significant decrease in the striatal uptake of 99Tcm-TRODAT-1 compared to healthy volunteers, and the ST/CB ratios were closely related to the stage of PD. The present study demonstrates that it is possible to visualize and quantify changes in dopamine transporter in the striatum of patients with PD using 99Tcm-TRODAT-1 and SPECT with good correlation to H/Y stage and unified Parkinson's disease rating scale (UPDRS) scale.     

Effects of subthalamic nucleus stimulation on striatal dopaminergic transmission in patients with Parkinson’s disease within one-year follow-up

The mechanisms by which deep brain stimulation (DBS) of the subthalamic nucleus (STN) leads to clinical benefit in Parkinson's disease (PD), especially with regard to dopaminergic transmission, remain unclear. Therefore, the objective of our study was to evaluate alterations of synaptic dopaminergic signaling following bilateral STN-DBS in advanced PD within a one-year follow-up. We used [(123)I]FP-CIT single-photon emission computed tomography (SPECT) to measure dopamine transporter (DAT) availability and [(123)I]IBZM SPECT to assess dopamine D(2) receptor (D2R) availability (stimulator ON condition).Patients (n=18) showed a tendency towards a better suppression of symptoms after STN-DBS (Unified Parkinson's Disease Rating Scale motor score with medication decreased from 24.1+/-16.1 to 15.4+/-7.45; p=0. 002) while medication was strongly reduced (61% reduction of levodopa equivalent units; p<0. 0001). No changes of striatal [(123)I]FP-CIT binding and an increase of [(123)I]IBZM binding up to 16% (p<0. 05) between pre-surgery and follow-up investigations were noticed. These data show that clinical improvement and reduction of dopaminergic drugs in patients with advanced PD undergoing bilateral STN-DBS are paralleled by stable DAT and recovery of striatal D2R availability 12 months after surgery.     

Correlation between fine motor activity and striatal dopamine D2 receptor density in patients with schizophrenia and healthy controls

Striatal dopamine D2 receptor density is an important indicator of many neuropsychiatric disorders and also of motor activity. This study examined the relationship between a fine motor task (finger tapping test, FTT) and striatal D2 dopamine receptor density by examining 20 healthy volunteers and 20 schizophrenic patients. Striatal D2 receptor density was determined with single photon emission computed tomography using [123I]IBZM (iodo-benzamide). The correlation between the FTT score and striatal D2 receptor density was statistically significant not only in the patient group but also in healthy controls. The FTT scores and striatal D2 receptor density were lower in medicated patients than that in healthy controls. Compared with the Simpson-Angus Scale scores, the FTT scores were more strongly associated with striatal D2 receptor density. The use of neuroleptic medication seemed to influence the associations between FTT scores and striatal D2 receptor density in the patient group. The FTT scores and striatal D2 receptor density were age-sensitive in healthy controls. FTT may be a more sensitive tool for detecting neuroleptic-induced motor impairment in patients with schizophrenia. The sensitivity of the FTT to age and neuroleptic effects may be explained in part by a decline in dopamine D2 density.     

Differentiating multiple system atrophy from Parkinson's disease: contribution of striatal and midbrain MRI volumetry and multi-tracer PET imaging

OBJECTIVES: The differential diagnosis between typical idiopathic Parkinson's disease (PD) and the striatonigral variant of multiple system atrophy (MSA-P) is often difficult because of the presence of signs and symptoms common to both forms of parkinsonism, particularly at symptom onset. This study investigated striatal and midbrain findings in MSA-P and PD patients in comparison with normal controls with the use of positron emission tomography (PET) and three dimensional magnetic resonance imaging (3D MRI) based volumetry to increase the differential diagnostic accuracy between both disease entities. METHODS: Nine patients with MSA-P, 24 patients with PD, and seven healthy controls were studied by MRI and PET with 6-[(18)F]-fluoro-L-dopa (FDOPA), [(18)F]fluoro-deoxyglucose (FDG), and 11-C-Raclopride (RACLO). Striatal and extrastriatal volumes of interest (VOI) were calculated on the basis of the individual MRI data. The PET data were transferred to the VOI datasets and subsequently analysed. RESULTS: MSA-P differed significantly from PD patients in terms of decreased putaminal volume, glucose metabolism, and postsynaptic D2 receptor density. The striatal FDOPA uptake was equally impaired in both conditions. Neither MRI volumetry nor PET imaging of the midbrain region further contributed to the differential diagnosis between PD and MSA-P. CONCLUSIONS: The extent and spatial distribution of functional and morphological changes in the striatum permit the differentiation of MSA-P from PD. Both, multi-tracer PET and 3D MRI based volumetry, may be considered equivalent in the assessment of different striatal abnormality in both disease entities. In contrast, MRI and PET imaging of the midbrain does not provide a further gain in diagnostic accuracy.     

~(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。     

In vivo measurement of haloperidol affinity to dopamine D2/D3 receptors by [123I]IBZM and single photon emission computed tomography.

This study examines the feasibility of a steady-state bolus-integration method with the dopamine D2/D3 receptor single photon emission computer tomography (SPECT) tracer, [123I]IBZM, for determination of in vivo affinity of haloperidol. The nonspecific binding of [123I]IBZM was examined in the rat brain by infusion of haloperidol to plasma levels approximately 100 times the Kd level in man. In humans, Kd for haloperidol binding was measured in four healthy volunteers that were examined twice: once with partial dopamine D2/D3 receptor blockade obtained by a scheduled infusion of unlabeled haloperidol (0.7 mg total dosage), and once in an unblocked state. Blood sampling and SPECT were performed intermittently during 6 hours after intravenous [123I]IBZM bolus injection. Plasma [123I]IBZM was determined by octane extraction. Plasma haloperidol was determined by a radioimmunoassay, and plasma protein binding was determined by equilibrium dialysis. In humans, the striatal D2/D3 receptor occupancy was 0.27+/-0.085 and the in vivo Kd for haloperidol was 0.25+/-0.1 nmol/L, which is comparable to Kd values as obtained from in vitro studies. The authors conclude that steady-state [123I]IBZM SPECT studies allow for determination of dopamine D2/D3 receptor occupancy in striatum and in vivo measurement of drug affinity to striatal dopamine D2 and D3 receptors.