[123I] FP‐CIT spect study in vascular parkinsonism and Parkinson's disease

There is substantial evidence to support a role for small vessel disease (SVD) as a cause for vascular parkinsonism (VP). Using [¹²³I] FP‐CIT SPECT (single photon emission computed tomography), we have tried to determine whether VP patients have pre‐synaptic dopaminergic function similar to PD patients, and whether the severity of parkinsonian symptoms as well as the levodopa response in VP patients are correlated with pre‐synaptic dopaminergic dysfunction. Thirteen patients fulfilling operational clinical criteria for VP had [¹²³I] FP‐CIT scans. Mean [¹²³I] FP‐CIT uptake in the basal ganglia was significantly lower in VP patients than in healthy controls, and the asymmetry index was not significantly different between these groups. In contrast, compared with the PD group, only the mean asymmetry index was significantly lower in VP patients. None of the parameters measured was significantly different between VP patients who had an insidious onset of parkinsonism (VPi) and those who had an acute onset (VPa). There was a significant correlation between the bilateral basal ganglia FP‐CIT uptake reduction in the VP patients and UPDRS motor scores, but not with the mean % reduction in motor UPDRS after levodopa. We suggest that in the majority of VP patients, pre‐synaptic dopaminergic function is reduced. The presence of a rather symmetrical FP‐CIT uptake in the basal ganglia may help to distinguish VP from PD and could therefore be used as a criterion for the clinical diagnosis of VP. © 2007 Movement Disorder Society     

Gray matter correlates of dopaminergic degeneration in Parkinson's disease: A hybrid PET/MR study using 18F‐FP‐CIT

Dopaminergic degeneration is a hallmark of Parkinson's disease (PD), which causes various symptoms affected by corticostriatal circuits. So far, the relationship between cortical changes and dopamine loss in the striatum is unclear. Here, we evaluate the gray matter (GM) changes in accordance with striatal dopaminergic degeneration in PD using hybrid PET/MR. Sixteen patients with idiopathic PD underwent ¹⁸F‐FP‐CIT PET/MR. To measure dopaminergic degeneration in PD, binding ratio (BR) of dopamine transporter in striatum was evaluated by ¹⁸F‐FP‐CIT. Voxel‐based morphometry (VBM) was used to evaluate GM density. We obtained voxelwise correlation maps of GM density according to the striatal BR. Voxel‐by‐voxel correlation between BR maps and GM density maps was done to evaluate region‐specific correlation of striatal dopaminergic degeneration. There was a trend of positive correlation between striatal BR and GM density in the cerebellum, parahippocampal gyri, and frontal cortex. A trend of negative correlation between striatal BR and GM density in the medial occipital cortex was found. Voxel‐by‐voxel correlation revealed that the positive correlation was mainly dependent on anterior striatal BR, while posterior striatal BR mostly showed negative correlation with GM density in occipital and temporal cortices. Decreased GM density related to anterior striatal dopaminergic degeneration might demonstrate degeneration of dopaminergic nonmotor circuits. Furthermore, the negative correlation could be related to the motor circuits of posterior striatum. Our integrated PET/MR study suggests that the widespread structural progressive changes in PD could denote the cortical functional correlates of the degeneration of striatal dopaminergic circuits. Hum Brain Mapp 37:1710–1721, 2016. © 2016 Wiley Periodicals, Inc .     

Functional brain imaging in pure akinesia with gait freezing: [18F] FDG PET and [18F] FP‐CIT PET analyses

Pure akinesia with gait freezing (PAGF) has characteristic features, including freezing of gait and prominent speech disturbance without rigidity or tremor. The purpose of this study was to investigate changes in brain glucose metabolism and presynaptic dopaminergic function in PAGF. By using [¹⁸F] fluorodeoxyglucose (FDG) PET, 11 patients with PAGF were compared with 14 patients with probable progressive supranuclear palsy (PSP), 13 patients with Parkinson's disease (PD), and 11 normal controls. [¹⁸F] N‐(3‐fluoropropyl)‐2β‐carbon ethoxy‐3β‐(4‐iodophenyl) nortropane (FP‐CIT) PET was performed in 11 patients with PAGF and with 10 normal controls. The PAGF patients showed decreased glucose metabolism in the midbrain when compared with normal controls. PSP patients showed a similar topographic distribution of glucose hypometabolism with additional areas, including the frontal cortex, when compared with normal controls. The FP‐CIT PET findings in patients with PAGF revealed severely decreased uptake bilaterally in the basal ganglia. These findings suggest that both PAGF and PSP may be part of the same pathophysiologic spectrum of disease. However, the reason why PAGF manifests clinically in a different manner needs to be further elucidated. © 2008 Movement Disorder Society     

Severity of neuropsychiatric symptoms and dopamine transporter levels in dementia with Lewy bodies: A 123I‐FP‐CIT SPECT study

Neuropsychiatric symptoms are frequent in dementia with Lewy bodies (DLB). Dopamine transporter (DAT) imaging with ¹²³I‐labeled ligand N‐δ‐(fluoropropyl)‐2β‐carbomethoxy‐3β‐(4‐iodophenyl)tropene (¹²³I‐FP‐CIT), which reliably measures midbrain dopaminergic dysfunction, has provided important evidence on the neurobiological substrate of some of these symptoms including apathy and depression. However, little is known on DAT levels and other distressing symptoms such as delusions and hallucinations. Therefore, ¹²³I‐FP‐CIT imaging was performed in 18 well‐characterized patients with DLB, and striatal DAT levels were correlated with the frequency/severity ratings of several neuropsychiatric symptoms. A wide range of neuropsychiatric symptoms could be observed in the sample. Significant correlations were observed between decreased striatal DAT levels and visual hallucinations. Although there were no correlations between striatal DAT levels and other neuropsychiatric symptoms, when considering the putamen and the caudate nucleus separately, delusions, depression, and apathy were inversely correlated to decreased caudate DAT levels. Theseresults provide intriguing evidence on the involvement of the mesocortical dopaminergic pathways in neuropsychiatric symptoms in DLB. © 2009 Movement Disorder Society     

Parkinson's disease is overdiagnosed clinically at baseline in diagnostically uncertain cases: A 3‐year European multicenter study with repeat [123I]FP‐CIT SPECT

Overdiagnosis of Parkinson's disease (PD) is suggested by specialist review of community diagnosis, and in postmortem studies. In specialist centers 4 to 15% of patients entered into clinical trials as early PD do not have functional imaging support for a PD diagnosis. In a European multicenter, prospective, longitudinal study, we compared clinical diagnosis with functional SPECT imaging using [¹²³I]FP‐CIT (DaTSCAN?, GE Healthcare). Repeat observations were performed over 3 years in patients with tremor and/or parkinsonism in whom there was initial diagnostic uncertainty between degenerative parkinsonism and nondegenerative tremor disorders. Video‐recording of clinical features was scored independently of functional imaging results by two blinded clinicians at 36 months (= gold standard clinical diagnosis). Three readers, unaware of the clinical diagnosis, classified the images as normal or abnormal by visual inspection. The main endpoint was the sensitivity and specificity of SPECT imaging at baseline compared with the gold standard. In 99 patients completing the three serial assessments, on‐site clinical diagnosis overdiagnosed degenerative parkinsonism at baseline in diagnostically uncertain cases compared with the gold standard clinical diagnosis (at 36 months), the latter giving a sensitivity of 93% and specificity of 46%. The corresponding baseline [¹²³I]FP‐CIT SPECT results showed a mean sensitivity of 78% and a specificity of 97%. Inter‐reader agreement for rating scans as normal or abnormal was high (Cohen's = 0.94–0.97). © 2008 Movement Disorder Society     

[123I]FP‐CIT SPET imaging in drug‐induced Parkinsonism

We assessed the status of dopamine nerve terminals in patients treated with dopamine receptor blocking agents (DRBAs) who had developed drug‐induced parkinsonism (DIP). We performed [¹²³I]FP‐CIT SPET in 32 consecutive patients who were on DRBAs for at least 6 months and developed extrapyramidal signs. The UPDRS‐III was used to assess clinical severity. Twenty‐six age‐ and sex‐matched healthy subjects served as control group. Putamen [¹²³I]FP‐CIT SPET binding was reduced in 14 and normal in the remaining 18 patients. There was no difference between the two groups for age, duration of DRBAs treatment, UPDRS III, tremor, rigidity, and bradykinesia subscores for upper and lower limbs. Conversely, symmetry of parkinsonian signs and presence bucco‐linguo‐masticatory dyskinesias were more frequent in individuals with normal tracer binding. Imaging of the dopamine transporter may help to identify subjects with DIP secondary to a loss of dopamine nerve terminals. © 2008 Movement Disorder Society     

(123) I]FP-CIT-SPECT asymmetry index to differentiate Parkinson's disease from vascular parkinsonism

Contrafatto D, Mostile G, Nicoletti A, Dibilio V, Raciti L, Lanzafame S, Luca A, Distefano A, Zappia M. [¹²³I]FP‐CIT‐SPECT asymmetry index to differentiate Parkinson’s disease from vascular parkinsonism.
Acta Neurol Scand: 2012: 126: 12–16.
© 2011 John Wiley & Sons A/S. Objectives – Differential diagnosis between vascular parkinsonism (VP) and Parkinson’s Disease (PD) is often difficult, due to the overlap in clinical presentation and the lack of specificity at neuroimaging. Aim of the study was to identify a possible reliable marker at SPECT imaging useful to distinguish the two conditions. Material and methods – We studied 20 PD, 20 VP and 20 essential tremor (ET) patients as control group, who had undergone a cerebral [¹²³I] FP‐CIT SPECT. A semiquantitative analysis was performed on DaTSCAN SPECT imaging and to establish the degree of asymmetry of the ligand uptake the Striatal Asymmetry Index (SAI) was used. Results – The binding of the ligand in the most affected side resulted significantly lower in VP than in ET patients but higher compared to PD patients. SAI was significantly higher in PD compared to VP (P < 0.001) and ET (P < 0.001) groups. We found that a cut‐off of SAI greater than 14.08 could differentiate PD from VP with a 100% specificity and a 50% sensitivity. Conclusions – SAI detected using [¹²³I]FP‐CIT SPECT can be used to differentiate VP and PD with a good degree of certainty.     

Differences in nigro‐striatal impairment in clinical variants of early Parkinson’s disease: evidence from a FP‐CIT SPECT study

Introduction: In idiopathic Parkinson’s disease (PD), two different clinical phenotypes are usually distinguished: a tremor dominant variant (TD) and an akinetic‐rigid type (ART). TD patients are characterized by a slower disease progression and a minor cognitive impairment. Striatal density of DAT, as quantified by FP‐CIT SPECT, has been reported to correlate with rigidity and akinesia but not with tremor. Objective: To evaluate FP‐CIT uptake in TD and ART phenotypes. Methods: We retrospectively evaluated from our database the pre‐synaptic nigro‐striatal function of 24 patients with TD‐PD and 38 patients with ART‐PD who underwent a FP‐CIT SPECT within 1 year from disease onset. Results: Disease duration, age at the time of SPECT scan and disease severity as measured with Unified Parkinson’s Disease Rating scale part III (UPDRS III) were not statistically different between the two groups. Putamen contralateral to the most clinically affected side showed a lower FP‐CIT uptake in ART patients compared to TD patients. No statistically significant differences emerged when considering bilateral caudate and ipsilateral putaminal uptake, as well as asymmetry indices and caudate/putamen ratios. FP‐CIT contralateral putaminal uptake correlated with the severity of rigidity and hypokinesia but not with tremor. Conclusions: These data suggest that other neurotransmitter systems apart from the nigro‐striatal dopaminergic system are involved in the generation of Parkinsonian tremor, and they are consistent with previous evidence of a lack of correlation between tremor severity and FP‐CIT uptake. Putaminal relative sparing in TD patients could partially explain the slower disease progression reported in this PD phenotype.     

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     

Striatal dopamine transporter imaging correlates with depressive symptoms and tower of London task performance in Parkinson's disease

We studied whether the ¹²³I‐FP‐CIT uptake in the striatum correlates with depressive symptoms and cognitive performance in patients with Parkinson's disease (PD). Twenty patients with PD without major depression and/or dementia (mean age 61.7 ± 12.7 years) underwent the ¹²³I‐FP‐CIT SPECT. Depressive symptoms and cognitive performance were assessed in the ON state. The ratios of striatal to occipital binding for the entire striatum, putamina, and putamen to the caudate (put/caud) index were calculated in the basal ganglia. The association between neuropsychiatric measures and dopamine transporter (DAT) availability was calculated; multiple regression analysis was used to assess association with age and disease duration. We found significant correlations between Montgomery and Asberg Depression Rating Scale (MARDS) and Tower of London (TOL) task scores and ¹²³I‐FP‐CIT uptake in various striatal ROIs. Multiple regression analysis confirmed the significant relationship between TOL performance and put/caud ratio (P = 0.001) and to age (P = 0.001), and between MADRS and left striatal (P = 0.005) and putaminal DAT availability (P = 0.003). Our pilot study results demonstrate that imaging with ¹²³I‐FP‐CIT SPECT appears to be sensitive for detecting dopaminergic deficit associated with mild depressive symptoms and specific cognitive dysfunction in patients with PD, yet without a current depressive episode and/or dementia. © 2008 Movement Disorder Society     

Midbrain serotonin transporters in de novo and L‐DOPA‐treated patients with early Parkinson’s disease – a [123I]‐ADAM SPECT study

Background: Dopaminergic availability is known to linearly decline in Parkinson’s disease (PD). In contrast, temporal characteristics of serotonergic markers like the serotonin transporter (SERT) in relation to clinical staging of PD and dopaminergic cell loss are less clear. This study investigated SERT availability using [¹²³I]‐ADAM and single‐photon emission tomography (SPECT) in drug‐naive, de novo patients, i.e., in a PD stage where dopaminergic decline starts to lead to the occurence of the characteristic motor symptoms. Methods: Nine de novo patients with PD and 9 age‐matched healthy controls were studied. Measurements were repeated after 3 months of levodopa treatment in patients with PD, and dopaminergic transporter (DAT) binding was examined at baseline using [¹²³I]‐FP‐CIT SPECT. Results: No alterations of SERT availability were found between groups, and neither correlation between SERT and DAT nor effects of levodopa treatment on SERT was found in patients with PD. Conclusions: These preliminary findings indicate that midbrain SERT is preserved in unmedicated patients at this early stage of PD, supporting the view that serotonergic decline temporally follows dopaminergic cell loss.     

Cognitive executive impairment and dopaminergic deficits in de novo Parkinson's disease

Cognitive impairment in Parkinson's disease (PD) is common and does directly impact patients' everyday functioning. However, the underlying mechanisms of early cognitive decline are not known. This study explored the association between striatal dopaminergic deficits and cognitive impairment within a large cohort of early, drug‐naïve PD patients and tested the hypothesis that executive dysfunction in PD is associated with striatal dopaminergic depletion. A cross‐sectional multicenter cohort of 339 PD patients and 158 healthy controls from the Parkinson's Progression Markers Initiative study was analyzed. Each individual underwent cerebral single‐photon emission CT (SPECT) and a standardized neuropsychological assessment with tests of memory as well as visuospatial and executive function. SPECT imaging was performed with [¹²³I]FP‐CIT, and specific binding ratios in left and right putamen and caudate nucleus were calculated. The association between specific binding ratios, cognitive domain scores, and age was analyzed using Pearson's correlations, partial correlation, and conditional process analysis. A small, but significant, positive association between total striatal dopamine transporter binding and the attention/executive domain was found (r = 0.141; P = 0.009) in PD, but this was not significant after adjusting for age. However, in a moderated mediation model, we found that cognitive executive differences between controls and patients with PD were mediated by an age‐moderated striatal dopaminergic deficit. Our findings support the hypothesis that nigrostriatal dopaminergic deficit is associated with executive impairment, but not to memory or visuospatial impairment, in early PD. © 2014 International Parkinson and Movement Disorder Society     

Dopaminergic deficit is not the rule in orthostatic tremor

Involvement of the dopaminergic system in orthostatic tremor is controversial. The aim of this study was to detect possible dopaminergic denervation in primary orthostatic tremor (OT). Twelve consecutive patients with a firm diagnosis of primary orthostatic tremor were compared with age‐matched normal controls. All the patients had a neurological examination, surface polymyography, and quantification of striatal dopamine transporters with ¹²³I‐FP‐CIT SPECT imaging. There was no significant difference in ¹²³I‐FP‐CIT SPECT findings between controls and patients with OT. Longstanding primary orthostatic tremor is not necessarily associated with ¹²³I‐FP‐CIT SPECT abnormalities, as 8 of our patients had more than a 10‐year history of OT. Primary orthostatic tremor without dopaminergic denervation remains a valid entity, although representing only a subtype of high‐frequency OT. A new role may emerge for ¹²³I‐FP‐CIT SPECT in distinguishing between patients whose symptoms will be restricted to OT throughout the disease course and patients at an increased risk of developing PD. © 2008 Movement Disorder Society     

Differential influence of propofol and isoflurane anesthesia in a non‐human primate on the brain kinetics and binding of [18F]DPA‐714, a positron emission tomography imaging marker of glial activation

Translocator protein 18 kDa (TSPO) expression at the mitochondrial membrane of glial cells is related to glial activation. TSPO radioligands such as [¹⁸F]DPA‐714 are useful for the non‐invasive study of neuroimmune processes using positron emission tomography (PET). Anesthetic agents were shown to impact mitochondrial function and may influence [¹⁸F]DPA‐714 binding parameters and PET kinetics. [¹⁸F]DPA‐714 PET imaging was performed in Papio anubis baboons anesthetized using either intravenous propofol (n = 3) or inhaled isoflurane (n = 3). Brain kinetics and metabolite‐corrected input function were measured to estimate [¹⁸F]DPA‐714 brain distribution (V_T). Displacement experiments were performed using PK11195 (1.5 mg/kg). In vitro [¹⁸F]DPA‐714 binding experiments were performed using baboon brain tissue in the absence and presence of tested anesthetics. Brain radioactivity peaked higher in isoflurane‐anesthetized animals compared with propofol (SUV_max = 2.7 ± 0.5 vs. 1.3 ± 0.2, respectively) but was not different after 30 min. Brain V_T was not different under propofol and isoflurane. Displacement resulted in a 35.8 ± 8.4% decrease of brain radioactivity under propofol but not under isoflurane (0.1 ± 7.0%). In vitro, the presence of propofol increased TSPO density and dramatically reduced its affinity for [¹⁸F]DPA‐714 compared with control. This in vitro effect was not significant with isoflurane. Exposure to propofol and isoflurane differentially influences TSPO interaction with its specific radioligand [¹⁸F]DPA‐714 with subsequent impact on its tissue kinetics and specific binding estimated in vivo using PET. Therefore, the choice of anesthetics and their potential influence on PET data should be considered for the design of imaging studies using TSPO radioligands, especially in a translational research context.     

Diagnostic value of brain MRI and 18F‐FDG PET in the differentiation of parkinsonian type multiple system atrophy from Parkinson’s disease

Background and purpose: Differentiation between parkinsonian type multiple system atrophy (MSA‐P) and Parkinson’s disease (PD) is important but often difficult. We investigated the diagnostic value of brain magnetic resonance imaging (MRI) and ¹⁸F‐fluorodeoxyglucose positron emission tomography (¹⁸F‐FDG PET) in differentiating MSA‐P from PD. Methods: Twenty‐four patients with MSA‐P (16 probable and 8 possible) and eight patients with PD were included in this study. Results: For analysis using the putaminal findings, the sensitivities were 58.3% by visual analysis of brain MRI, 95.8% by visual analysis of ¹⁸F‐FDG PET, and 79.2% by statistical parametric mapping (SPM) analysis of ¹⁸F‐FDG PET in differentiating MSA‐P from PD; the specificity was 100% for each analysis. Using the putaminal findings, visual analysis of ¹⁸F‐FDG PET had a higher sensitivity compared with brain MRI (P = 0.004) and SPM analysis of ¹⁸F‐FDG PET revealed a tendency towards higher sensitivity compared with brain MRI (P = 0.063). For analysis using both putaminal and infratentorial findings, the sensitivities were 79.2% by visual analysis of brain MRI, 95.8% by visual analysis of ¹⁸F‐FDG PET, 95.8% by SPM analysis of ¹⁸F‐FDG PET in differentiating MSA‐P from PD; the specificity was 100% for each analysis. Conclusion: Both brain MRI and ¹⁸F‐FDG PET showed diagnostic usefulness in differentiating MSA‐P from PD, with ¹⁸F‐FDG PET being more sensitive than brain MRI.     

Cognitive‐nigrostriatal relationships in de novo,drug‐naïve Parkinson's disease patients: A [I‐123]FP‐CIT SPECT study

To unveil cognitive‐nigrostriatal correlations in Parkinson's disease (PD), 30 de novo, drug‐naïve PD patients and 15 patients with essential tremor (Controls, CTR) underwent a neuropsychological (NPS) battery and brain SPECT with [I‐123]Ioflupane, as a biomarker of nigrostriatal function. Automatic extraction of uptake at caudate and putamen level was conducted through the BasGan software, also allowing partial volume effect correction. Because of the multicollinearity among neuropsychological tests and among SPECT variables, factor analysis was applied to 16 neuropsychological scores; moreover, the four SPECT variables were merged into a mean SPECT value (mSPECT). Factor analysis identified four NPS factors: a dys‐executive (NPS‐EX), a visuospatial (NPS‐VS), a verbal memory (NPS‐VM), and a “mixed” (NPD‐MIX) factor. In PD group, there were inverse correlations between UPDRS‐III score and both NPS‐VS (P < 0.01) and mSPECT (P < 0.05), and a direct correlation between mSPECT and NPS‐EX (P < 0.05). Post hoc analysis showed a direct correlation between NPS‐EX and caudate uptake in both hemispheres (P < 0.05). Moreover, inverse correlations were found between UPDRS‐III and, respectively, putamen uptake in the less affected hemisphere (P < 0.01), and putamen and caudate uptake in the more affected hemisphere (P < 0.05). In CTR, no correlation was found between mSPECT and either NPS or GDS values. Nigro‐caudate function affects executive capabilities in PD but not in CTR, which appears to be unrelated to the disease motor severity at its onset. Instead, PD motor severity is related to nigro‐putaminal impairment and visuospatial dysfunction. The role of these data as predictive features of cognitive decline and eventually dementia remains to be established in longitudinal studies. © 2010 Movement Disorder Society     

Evaluation of (‐)‐[18F]Flubatine‐specific binding: Implications for reference region approaches

We aimed to characterize changes in binding of (‐)‐[¹⁸F]Flubatine to α₄β₂*‐nicotinic acetylcholine receptors (α₄β₂*‐nAChRs) during a tobacco cigarette smoking challenge. Displacement of (‐)‐[¹⁸F]Flubatine throughout the brain was quantified as change in (‐)‐[¹⁸F]Flubatine distribution volume (V_T), with particular emphasis on regions with low V_T. Three tobacco smokers were imaged with positron emission tomography (PET) during a 210 min bolus‐plus‐constant infusion of (‐)‐[¹⁸F]Flubatine. A tobacco cigarette was smoked in the PET scanner ～125 min after the start of (‐)‐[¹⁸F]Flubatine injection. Equilibrium analysis was used to estimate V_T at baseline (90‐120 min) and after cigarette challenge (180‐210 min), at the time of greatest receptor occupancy by nicotine. Smoking reduced V_T by 21 ± 9% (average ±SD) in corpus callosum, 17 ± 9% in frontal cortex, 36 ± 11% in cerebellum, and 22 ± 10% in putamen. The finding of displaceable (‐)‐[¹⁸F]Flubatine binding throughout the brain is an important consideration for reference region‐based quantification approaches with this tracer. We observed displacement of (‐)‐[¹⁸F]Flubatine binding to α₄β₂*‐nicotinic acetylcholine receptors in corpus callosum by a tobacco cigarette challenge. We conclude that reference region approaches utilizing corpus callosum should first perform careful characterization of displaceable (‐)‐[¹⁸F]Flubatine binding and nondisplaceable kinetics in this putative reference region.     

Striatal dopamine transporter in different disability stages of Parkinson's disease studied with [I]β-CIT SPECT

Six healthy controls and eighteen patients with Parkinson's disease in different disability stages were studied with SPECT using [¹²³I]β-CIT to label the striatal dopamine transporter. The mean uptake of [¹²³I]β-CIT in the putamen was reduced to 54% of the control mean and to 65% of the average control value in the caudate nucleus. In patients with totally, or predominantly unilateral symptoms the reduction was greater on the side opposite to the predominant symptoms (to 56% of the control mean in the contralateral putamen and to 77% in the ipsilateral putamen).There was a significant negative correlation between [¹²³I]β-CIT uptake in the putamen and the Hoehn and Yahr stage (r = -0.81, p < 0.0001). An analysis of covariance was performed using age and disease duration as covarianes, and the correlation between putaminal [¹²³I]β-CIT uptake and parkinsonian disability according to the Hoehn and Yahr stage remained significant (r = -0.75, P = 0.02). A similar correlation was seen in the caudate nucleus (r = −0.79, p < 0.0001) between the uptake of [¹²³I]β-CIT and the Hoehn and Yahr stage. The correlation also remained significant after correction for the duration of disease and age of the patients (r= -0.76, P = 0.02).The present results show that [1231],Q-CIT SPECT is a useful method to study the function of presynaptic dopaminergic terminals in PD, and might be used in the early diagnosis and follow-up of the disease.     

The implication of nigrostriatal dopaminergic degeneration in the pathogenesis of REM sleep behavior disorder

Background and purpose: The pathogenesis of rapid eye movement (REM) sleep behavior disorder (RBD) is not clear despite its frequent association with Parkinson’s disease (PD). We investigated whether the nigrostriatal dopaminergic system is involved in the development of idiopathic RBD. Methods: Fourteen patients with RBD, 14 patients with PD and 12 normal controls were included in the study. The diagnosis of RBD was confirmed on polysomnography. All the participants performed single‐photon emission computed tomography imaging 3 h after injection of [¹²³I]FP‐CIT. During REM sleep of the RBD patients, each 30‐s epoch was rated as ‘tonic’ when there was at least 50% of tonically maintained chin electromyography (EMG) activity in the epoch. Phasic EMG activities were calculated as the percentage of 3‐s mini‐epoch containing phasic EMG events (leg and chin, separately). Results: The RBD patients showed a trend of lower binding in the striatum than the normal controls (P = 0.07), and the significance was revealed in the putamen (P = 0.02). However, in 11 individual cases of the 14 RBD patients, the dopamine transporter (DAT) densities in the putamen still remained within the normal range. In the RBD patients, there was no correlation between EMG activities and DAT densities. Conclusions: Nigrostriatal dopaminergic degeneration could be a part of the pathogenesis of RBD, but not essential for the development of RBD. The lack of correlation between RBD severity and DAT densities suggests that another pathogenic process not related to nigrostriatal dopaminergic transmission may be implicated in RBD.     

A dual‐tracer study of extrastriatal 6‐[18F]fluoro‐m‐tyrosine and 6‐[18F]‐fluoro‐l‐dopa Uptake in Parkinson's disease

6‐[¹⁸F]‐Fluoro‐l ‐dopa (FDOPA) has been widely used as a biomarker for catecholamine synthesis, storage, and metabolism—its intense uptake in the striatum, and fainter uptake in other brain regions, is correlated with the symptoms and pathophysiology of Parkinson's disease (PD). 6‐[¹⁸F]fluoro‐m‐tyrosine (FMT), which also targets l ‐amino acid decarboxylase, has potential advantages over FDOPA as a radiotracer because it does not form catechol‐O‐methyltransferase (COMT) metabolites. The purpose of the present study was to compare the regional distribution of these radiotracers in the brains of PD patients. Fifteen Parkinson's patients were studied with FMT and FDOPA positron emission tomography (PET) as well as high‐resolution structural magnetic resonance imaging (MRI). MRI's were automatically parcellated into neuroanatomical regions of interest (ROIs) in Freesurfer ( http://surfer.nmr.mgh.harvard.edu ); region‐specific uptake rate constants (K_occ) were generated from coregistered PET using a Patlak graphical approach. The essential findings were as follows: (1) regional K_occ were highly correlated between the radiotracers and in agreement with a previous FDOPA studies that used different ROI selection techniques; (2) FMT K_occ were higher in extrastriatal regions of relatively large uptake such as amygdala, pallidum, brainstem, hippocampus, entorhinal cortex, and thalamus, whereas cortical K_occ were similar between radiotracers; (3) while subcortical uptake of both radiotracers was related to disease duration and severity, cortical uptake was not. These results suggest that FMT may have advantages for examining pathologic changes within allocortical loop structures, which may contribute to cognitive and emotional symptoms of PD. Synapse 68:325–331, 2014 . © 2014 Wiley Periodicals, Inc.