A single photon emission computed tomography scan study of striatal dopamine D2 receptor binding with 123I-epidepride in patients with schizophrenia and controls.

The usefulness of 123I-epidepride as a single photon emission computed tomography (SPECT) scan D2 receptor ligand was examined in vivo in 13 medicated patients with schizophrenia and age- and sex-matched normal controls. To establish the effect of endogenous dopamine on 123I-epidepride binding, 4 of the 13 controls also received 20 mg D-amphetamine. The results showed that 123I-epidepride had high specific binding to the striatum in both patients with schizophrenia and normal controls. There was a trend for the total striatal binding of medicated patients with schizophrenia, as measured by total basal ganglia: frontal cortex (TBG:FC) ratios, to be less than the binding of controls (P = 0.053). This trend confirms previous work showing that antipsychotic medication decreases the number of D2 receptors available for binding to the radioligand. Interestingly, there was also a significant relationship between 123I-epidepride binding ratios and global functioning scales (Global Assessment of Functioning scale [GAF]) for schizophrenia (r = 0.56, P = 0.045), although there was no such relationship with the Brief Psychiatric Rating Scale (BPRS). In addition, our results showed that amphetamine-induced dopamine release did not alter 123I-epidepride binding, confirming the high specific binding of 123I-epidepride to the D2 receptor. We conclude that 123I-epidepride appears to be a very useful SPECT ligand for imaging the D2 receptor.     

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.     

Striatal D2/D3 receptor occupancy, clinical response and side effects with amisulpride: an iodine-123-iodobenzamide SPET study

INTRODUCTION: Amisulpride appears to be an effective atypical agent for treating schizophrenia in a dose-dependent manner. METHODS: 29 patients suffering from schizophrenia or schizoaffective disorder were treated with a broad dose range of amisulpride (50-1 200 mg/day, mean: 455.2+/-278.8 mg/day). After 2 weeks, brain single photon emission tomography (SPET) scans were performed two hours after intravenous injection of 185 MBq [ (123)I]IBZM. Clinical evaluations and ratings of extrapyramidal symptoms were performed at baseline and after steady state treatment of two weeks with amisulpride. RESULTS: In patients treated with amisulpride, specific binding of [ (123)I]IBZM to D2 receptors was significantly decreased (p<0.001) compared to healthy controls. D2 receptor blockade correlated well with administered doses and plasma concentrations of amisulpride. Extrapyramidal side effects, which had to be treated with biperiden, were observed in 31% of the patients. Clinical response was very good, without correlation between the response and striatal D2 occupancy. DISCUSSION: Within the first two weeks of treatment with the atypical antipsychotic amisulpride a significant occupancy of striatal postsynaptic dopamine D2 receptors was achieved. At the same time amisulpride shows an excellent tolerability with good efficacy.     

Dopamine D2 receptor occupancy measured by single photon emission computed tomography with 123I-Iodobenzamide in chronic schizophrenia

Single photon emission computed tomography (SPECT) with 123I-iodobenzamide (123I-IBZM) was used to study 22 chronic schizophrenic patients. The patients, who were receiving maintenance therapy with typical neuroleptics, had not shown any significant improvement since their admission to the hospital. Basal ganglia/frontal cortex ratios of the uptake of 123I-IBZM did not show significant differences on the basis of neuroleptic dosage in chlorpromazine equivalents. There were, however, significant differences in 123I-IBZM uptake in the basal ganglia among patients characterized by negative, mixed, and positive symptoms of schizophrenia. Although only a small number of patients had shown a positive response to treatment by the time of discharge, D2 receptor blockade was significantly higher in responders than in nonresponders. In addition, there was an inverse correlation between reduced activation as measured by the Brief Psychiatric Rating Scale and the basal ganglia/frontal cortex ratio. These findings suggest a complex pathogenetic link between the blockade of dopamine D2 receptors and psychopathology in chronic schizophrenic patients. SPECT studies with 123I-IBZM appear to have prognostic value in identifying chronic schizophrenic patients who respond poorly to neuroleptic treatment.     

应用单光子发射计算机体层摄影术研究药物滥用对人脑纹状体多巴胺转运体的损害

目的　在分子水平上研究摇头丸和海洛因滥用对人脑纹状体多巴胺转运体(DAT)的损害。方法　对健康对照组21名、摇头丸组12例、海洛因组43例进行单光子发射计算机体层摄影术检测。静脉注射显像剂99Tcm TRODAT 1剂量为740MBq/ml。计算纹状体的体积、质量、纹状体与全脑放射性比值(Ra% )和差值率(% )。结果　对照组双侧纹状体呈典型“熊猫眼”形,双侧尾状核和豆状核大致等大,DAT分布均匀、对称。摇头丸组和海洛因组纹状体的体积分别为(21 4±4 5)cm3 和(21 3±4 4)cm3,小于对照组[ ( 32 0±2 2 )cm3;P<0 01 ];质量分别为( 23 7±3 9 )g和( 22 4±3 2)g,低于对照组[ (33 6±2 6)g;P<0 01];Ra%分别为(5 9±0 8)%和(5 2±0 9)%,亦低于对照组[ (7 6±2 0)%;P<0 05],摇头丸组和海洛因组纹状体与全脑放射性比值与对照组的差值率分别是22 03%和30 74%。结论　滥用摇头丸和海洛因均破坏脑纹状体多巴胺能神经元的功能,DAT的数量、密度、分布和活性减低。     

抑郁症患者的脑单光子发射计算机断层摄影研究

为观察抑郁症患者局部脑血流（ｒＣＢＦ）情况，对１１例处于症状发作期的抑郁症患者及１３名正常对照者用９９ｍＴｃ标记的亚锡双半胱乙脂进行脑单光子发射电子计算机断层摄影（ＳＰＥＣＴ）。结果显示，观察组与对照组比较，左下额、左前颞及扣带皮质的ｒＣＢＦ显著下降（Ｐ＜０．０１），而右上额、右下额和两侧顶叶、枕叶的ｒＣＢＦ也有下降（Ｐ＜０．０５）。观察组尚存在上额皮质ｒＣＢＦ两侧非对称性（Ｐ＜０．０５），而对照组未见相应的非对称性。提示抑郁症发作时存在某些脑功能区ｒＣＢＦ下降以及两侧脑功能区局部的ｒＣＢＦ不对称性。     

Cognitive deficits and striatal dopaminergic denervation in Parkinson's disease: a single photon emission computed tomography study using 123iodine-beta-CIT in patients on and off levodopa

Cognitive deficits affecting executive (frontal) functions have been widely described in Parkinson's disease (PD). However, dopa therapies are generally ineffective at reversing these deficits, except for tasks involving a sharing of attention such as working memory or simultaneous processing tasks. The aim of this study was to assess the relation between the nigrostriatal dopaminergic denervation in PD, as measured by SPECT with (123)Iodine-beta-CIT and the cognitive deficits, as measured by a simultaneous processing task, which had already been shown to be sensitive to dopa treatment. Ten patients with PD and ten control subjects were selected and matched for age, sex, and education. All subjects were assessed using computed visuo-auditory tasks which allow for the measurement of three cognitive processing conditions: 1) a Selective Processing Time; 2) a Competitive Processing Time; and 3) a Simultaneous Processing Time. Patients with PD were assessed both with (ON) and without (OFF) their usual dopaminergic treatment. The simultaneous processing condition but not the selective or the competitive conditions took significantly more time for patients with PD OFF than for either the control subjects or the patients with PD ON. In addition, when patients with PD were OFF, the simultaneous processing condition was correlated with the (123)Iodine-beta-CIT binding, but not when they were ON. These results suggest that nigrostriatal DA denervation may be involved in the specific impairment that patients with PD experience with simultaneous cognitive processing.     

Analysis of regional cerebral blood flow and distribution volume in Machado-Joseph disease by iodine-123I IMP single photon emission computed tomography]

Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar ataxia. Its clinical features vary greatly in different generations of the same family. Regional cerebral blood flow (rCBF) and distribution volume (Vd) in the pons, cerebellum, and cerebral cortex were measured in 12 patients with MJD by autoradiography (ARG) and the table look-up (TLU) method of iodine-123 IMP (123I-IMP) single photon emission computed tomography (SPECT). Representative cases were as follows: A 46-year-old woman first experienced gait ataxia at age 38. Computed tomography (CT) and magnetic resonance imaging (MRI) showed no atrophy in the pons or cerebellum, but rCBF measured by the 123I-IMP SPECT ARG method detected hypoperfusion in the pons, and cerebellar vermis and hemisphere. A 76-year-old woman first experienced gait ataxia at age 69. CT and MRI findings showed severe atrophy in the pons, and cerebellar vermis and hemisphere. Moreover, rCBF was decreased in the pons, whereas it was not decreased in the cerebellar vermis and hemisphere. In the pons of patients with MJD, rCBF was markedly decreased regardless of disease severity. Because this SPECT finding for the pons looked like a 'dot', we have called it the 'pontine dot sign'. In the MJD group, rCBF was significantly decreased in the pons (Student's t test, p < 0.01) and cerebellar vermis (p < 0.05). The Vd was also significantly decreased in the pons (p < 0.005) in comparison with that for normal subjects. Pearson's correlation analysis yielded a significant relationship between the rCBF in the pons and age at onset (r = 0.578, p < 0.05). There was a strong correlation between the Vd for the pons and age at onset (r = 0.59, p < 0.05). Pearson's correlation analysis also showed a significant relationship between the Vd in the cerebellar hemispheres and International Cooperative Ataxia Rating Scale (r = 0.644, p < 0.05). The pontine rCBFs in patients with early onset MJD, whose pons was not atrophic, decreased more than did those in patients with late onset MJD, whose pons was severely atrophic. This suggests that the SPECT findings are indicative of underlying neurodegenerative processes that began before the onset of clinical symptoms. Different processes seem to function in atrophy and the rCBF decrease in the pons of patients with MJD. These findings will be proved by the increase of the number of cases of MJD. Until now, there has been no report on rCBF and Vd obtained by 123I-IMP SPECT for patients with MJD identified by gene analysis. Our study shows that SPECT measurement of rCBF and Vd is useful for understanding the pathophysiology of MJD.     

The diagnosis of dementia with single photon emission computed tomography

Single photon emission computed tomography is a practical modality for the study of physiologic cerebral activity in vivo. We utilized single photon emission computed tomography and N-isopropyl-p-iodoamphetamine iodine 123 to evaluate regional cerebral blood flow in nine patients with Alzheimer's disease (AD), five healthy elderly control subjects, and two patients with multi-infarct dementia. We found that all subjects with AD demonstrated flow deficits in temporoparietal cortex bilaterally, and that the ratio of activity in bilateral temporoparietal cortex to activity in the whole slice allowed the differentiation of all patients with AD from both the controls and from the patients with multi-infarct dementia. Furthermore, this ratio showed a strong correlation with disease severity in the AD group. Single photon emission computed tomography appears to be useful in the differential diagnosis of dementia and reflects clinical features of the disease.     

Impact of dopamine transporter single photon emission computed tomography imaging using I-123 ioflupane on diagnoses of patients with parkinsonian syndromes

To assess the impact of I-123 ioflupane single photon emission computed tomography (SPECT) imaging on classifying patients with striatal dopaminergic deficits. Sixty-one patients with an initial diagnosis of parkinsonism or uncertain tremor disorder were screened and followed-up for one year. All patients were re-examined by two neurologists at our centre and were classified as having neurodegenerative or non-neurodegenerative disorders. Patients underwent I-123 ioflupane SPECT imaging. SPECT studies were blindly evaluated and classified as normal or abnormal (indicative of neurodegenerative disorders). The overall agreement of the SPECT imaging results with the initial classification was 65.6% (kappa = 0.229, p = 0.074) but was 90.2% (kappa = 0.782, p < 0.001) with the classification of the neurologists at our centre. I-123 ioflupane SPECT imaging is a valuable method in the evaluation of patients presenting clinically with uncertain parkinsonian syndromes or for whom diagnostic doubt exists.     

The distribution of cerebral muscarinic acetylcholine receptors in vivo in patients with dementia. A controlled study with 123IQNB and single photon emission computed tomography

A high-affinity muscarinic receptor antagonist, 123IQNB (3-quinuclidinyl-4-iodobenzilate labeled with iodine 123), was used with single photon emission computed tomography to image muscarinic acetylcholine receptors in 14 patients with dementia and in 11 healthy controls. High-resolution single photon emission computed tomographic scanning was performed 21 hours after the intravenous administration of approximately 5 mCi of IQNB. In normal subjects, the images of retained ligand showed a consistent regional pattern that correlated with postmortem studies of the relative distribution of muscarinic receptors in the normal human brain, having high radioactivity counts in the basal ganglia, occipital cortex, and insular cortex, low counts in the thalamus, and virtually no counts in the cerebellum. Eight of 12 patients with a clinical diagnosis of Alzheimer's disease had obvious focal cortical defects in either frontal or posterior temporal cortex. Both patients with a clinical diagnosis of Pick's disease had obvious frontal and anterior temporal defects. A region of interest statistical analysis of relative regional activity revealed a significant reduction bilaterally in the posterior temporal cortex of the patients with Alzheimer's disease compared with controls. This study demonstrates the practicability of acetylcholine receptor imaging with 123IQNB and single photon emission computed tomography. The data suggest that focal abnormalities in muscarinic binding in vivo may characterize some patients with Alzheimer's disease and Pick's disease, but further studies are needed to address questions about partial volume artifacts and receptor quantification.     

Relationship between SLC6A3 genotype and striatal dopamine transporter availability: a meta-analysis of human single photon emission computed tomography studies

The human dopamine transporter (DAT) gene (SLC6A3) contains a 40-bp variable number of tandem repeats (VNTR) polymorphism. A number of studies have investigated the association of this VNTR with striatal DAT availability in humans using single photon emission computed tomography (SPECT). However, the results are not consistent. Therefore, we carried out a meta-analysis of the association between the SLC6A3 VNTR and striatal DAT binding measured in human SPECT studies. The meta-analysis of five samples of healthy individuals failed to find a significant difference in DAT availability between SLC6A3 9-repeat carriers and 10-repeat homozygotes (P = 0.22) although the 9R carriers had nominally higher striatal DAT levels (g = 0.66). The results remained nonsignificant after the inclusion of patient samples, namely schizophrenia, attention deficit hyperactivity disorder, and Parkinson's disease (four samples; all P > 0.18). To conclude, this meta-analysis provides no evidence to support the hypothesis that the SLC6A3 VNTR is significantly associated with interindividual differences in DAT availability in the human striatum. Further work is needed to clarify the molecular mechanisms by which this polymorphism may affect cognition and psychiatric disorders, if not through altered expression as measured by molecular imaging.     

The role of brain single photon emission computed tomography in the diagnosis of primary progressive aphasia.

We present two cases of primary progressive aphasia studied with neuropsychologic measures, computed tomography or magnetic resonance imaging, and single-photon emission computed tomography with technetium Tc99m-labeled hexamethylpropyleneamine oxime. Clinical and neuropsychologic observations revealed a marked, progressive loss of language functions over time with relative preservation of nonlanguage cognitive functions in both patients. The brain single-photon emission computed tomographic scan revealed marked left frontal and minimal left temporal and parietal hypoperfusion in case 1 and marked left posterior frontal and minimal left temporal hypoperfusion in case 2. The value of brain single-photon emission computed tomography in distinguishing primary progressive aphasia from Alzheimer's disease is described.     

The current place of single photon emission computed tomography in epilepsy evaluations

Single photon emission computed tomography is appropriate for peri-ictal imaging inpatients with focal epilepsy being considered for surgical treatment.     

Positron emission tomography shows reduced striatal dopamine D1 but not D2 receptors in juvenile neuronal ceroid lipofuscinosis

We studied striatal dopamine D1 and D2 receptors in patients with juvenile neuronal ceroid lipofuscinosis (JNCL) with positron emission tomography (PET) using a dopamine D1 receptor antagonist [11C]NNC 756 and a dopamine D2 receptor antagonist [11C]raclopride as ligands. The mean [11C]NNC 756 uptake value in JNCL was reduced by 15 % from the mean control value in the putamen (p < 0.01) and by 13 % in the caudate nucleus (p < 0.01). The mean [11C]raclopride uptake in JNCL patients was not significantly different from the mean of the control group either in the putamen or the caudate nucleus. Our results show a mild reduction in striatal dopamine D1 but not in D2 receptors in JNCL, indicating slightly impaired striatal neuronal function. The contribution of these changes to the extrapyramidal symptoms of the patients and their treatment deserves further studies.     

Residual striatal dopaminergic nerve terminals in very long‐standing Parkinson's disease: A single photon emission computed tomography imaging study

Molecular imaging studies of Parkinson's disease (PD) progression mostly focus on the first 5 years after disease onset, demonstrating rapid initial nigrostriatal neuronal loss. The fate of residual functional dopaminergic nerve terminals in patients with long‐standing PD has not yet been specifically explored. Therefore, we performed [¹²³I]‐FP‐CIT single photon emission computed tomography (SPECT) in 15 patients with very long‐standing PD (mean disease duration 20.6 ± 6.3 years). Measurable uptake of [¹²³I]‐FP‐CIT was still detected in the striata of all patients. As seen in early stages, reduction of tracer uptake in the putamen was more prominent than in the caudate nucleus. Asymmetry in tracer uptake between the two putamen and caudate nuclei was preserved. These findings indicate that degeneration of dopaminergic neurons in PD is not total even after many years of illness. Data should be considered in exploring underlying causes of progressive loss of nigrostriatal dopaminergic neurons and development of future novel dopaminergic therapeutic strategies in PD. © 2010 Movement Disorder Society     

Hypofrontality revisited: a high resolution single photon emission computed tomography study in schizophrenia.

Hypofrontality or reduced activity in the prefrontal cortex, measured as reduced frontal perfusion or glucose uptake, has gained the status of an established finding in the medical literature on schizophrenia. Many relevant studies, however, have potential sources of bias, such as small subject numbers, or unreliable performance of activation tasks by the patients during the scanning procedure. Seventy patients with non-affective and non-organic psychoses were recruited--most qualifying for DSM III-R schizophrenia or schizophreniform psychosis (n = 60)--together with 20 healthy volunteers. They underwent single photon emission computed tomography with 99mTc-exametazime, carried out at rest. Tracer uptake was normalised to the occipital cortex. Group differences in tracer uptake were predicted in anterior regions of interest (prefrontal cortex and mesial frontal/cingulate cortex). Actively psychotic (including schizophrenic) patients not taking any drugs showed increased uptake in the prefrontal cortex. Reduced tracer uptake occurred in the mesial frontal cortex of schizophrenic patients, particularly if they were taking drugs. Relatively increased prefrontal tracer uptake associated with relatively decreased mesial frontal uptake characterised the patients in comparison with the controls. Generalised hypofrontality is, therefore, not a feature of schizophrenic patients at rest whether taking drugs or not.