Comparison of [123I]ß-CIT and [123I]IPCIT as single-photon emission tomography radiotracers for the dopamine transporter in nonhuman primates

Single-photon emission tomographic (SPET) imaging with the radiotracer [¹²³I]2-carbomethoxy-3-(4-iodophenyl)tropane ([¹²³I]-CIT) has been reported to be a useful in vivo measure of dopamine (DA) transporters. However, in addition to its high DA transporter affinity,-CIT also binds with high affinity to serotonin (5-HT) transporters. 2-Carboisopropoxy-3-(4-iodophenyl)tropane (IPCIT) has been demonstrated by in vitro studies to have higher selectivity for the DA transporter. We compared [¹²³I]-CIT and [¹²³I]IPCIT SPET imaging and plasma metabolite analyses in baboons to evaluate the potential advantages of [¹²³I]IPCIT for quantitative in vivo measurements of DA transporter densities. Both tracers had low levels (2% of total plasma¹²³I activity) of lipophilic radiolabeled metabolites at 420 min. [¹²³I]IPCIT had significantly higher binding to plasma proteins. The average percent free (nonprotein bound) [¹²³I]-CIT and [¹²³I]IPCIT were 52%±7% and 14%±6%, respectively. Region of interest uptake data were normalized by injected dose and body weight. Consistent with the high density of 5-HT transporters in the midbrain and the lower 5-HT transporter affinity of IPCIT, the normalized peak specific midbrain uptake of [¹²³I]-CIT (1.7±0.5) was higher than that of [¹²³I]IPCIT (0.4±0.2). Consistent with its greater lipophilicity, [¹²³I]IPCIT had higher nonspecific uptake, such that normalized cerebellar uptake of [¹²³I]IPCIT was about twice that of [¹²³I]-CIT. The ratio of specific to nonspecific uptake in striatum was greater for [¹²³I]-CIT compared to [¹²³I]IPCIT; however, striatal binding potentials and distribution volumes were not significantly different. In conclusion, [¹²³I]IPCIT demonstrated in vivo a higher DA transporter selectivity and higher level of nonspecific uptake.     

Impaired dopaminergic neurotransmission in patients with traumatic brain injury: a SPET study using 123I-β-CIT and 123I-IBZM

Structural imaging suggests that traumatic brain injury (TBI) may be associated with disruption of neuronal networks, including the nigrostriatal dopaminergic pathway. However, to date deficits in pre- and/or postsynaptic dopaminergic neurotransmission have not been demonstrated in TBI using functional imaging. We therefore assessed dopaminergic function in ten TBI patients using [¹²³I]2-#-carbomethoxy-3-#-(4-iodophenyl)tropane (#-CIT) and [¹²³I]iodobenzamide (IBZM) single-photon emission tomography (SPET). Average Glasgow Coma Scale score (-SD) at the time of head trauma was 5.8dž.2. SPET was performed on average 141 days (SD ᇰ) after TBI. The SPET images were compared with structural images using cranial computerised tomography (CCT) and magnetic resonance imaging (MRI). SPET was performed with an ADAC Vertex dual-head camera. The activity ratios of striatal to cerebellar uptake were used as a semiquantitative parameter of striatal dopamine transporter (DAT) and D2 receptor (D2R) binding. Compared with age-matched controls, patients with TBI had significantly lower striatal/cerebellar #-CIT and IBZM binding ratios (PА.01). Overall, the DAT deficit was more marked than the D2R loss. CCT and MRI studies revealed varying cortical and subcortical lesions, with the frontal lobe being most frequently affected whereas the striatum appeared structurally normal in all but one patient. Our findings suggest that nigrostriatal dysfunction may be detected using SPET following TBI despite relative structural preservation of the striatum. Further investigations of possible clinical correlates and efficacy of dopaminergic therapy in patients with TBI seem justified.     

Differential kinetics of [123I]β-CIT binding to dopamine and serotonin transporters

Iodine-123-labelled 3-(4-iodophenyl)tropane-2-carboxylic acid ([¹²³I]-CIT) labels both the dopamine transporter (DAT) and the serotonin transporter (5-HTT) and this ligand is able to clarify pathological changes in both dopaminergic and serotonergic systems. However, the differential kinetics of -CIT binding to DAT and 5-HTT has not been clarified fully. In this study we examined time-activity curves of [¹²³I]-CIT in individual regions in the rat brain. Using cerebellum as the reference region,k ₃ andk ₄ values were estimated by a two-compartment kinetic analysis. In the striatum, the kinetics was slowest among all brain areas. In this area specific binding reached its peak 4 h after the injection. In the hypothalamus, specific binding reached its peak 1 h after the injection and its amount did not change until 4 h after the injection. In the occipital cortex, the binding and washout of the ligand were fastest among all brain regions. Estimatedk ₃ values were 0.040±0.003 in the striatum, 0.019±0.002 in the hypothalamus and 0.082±0.011 in the occipital cortex (min^–t, mean ±SD). Estimatedk ₄ values were 0.0034±0.0005 in the striatum, 0.0071±0.0009 in the hypothalamus and 0.083±0.013 in the occipital cortex (min^–1, mean ±SD). Therefore binding kinetics of [¹²³I]-CIT in the region rich in DAT is apparently different from that in the region rich in 5-HTT. These results will provide fundamental data to image both DAT and 5-HTT in one series of examinations with [¹²³I]-CIT.     

Early-stage [123I]β-CIT SPECT and long-term clinical follow-up in patients with an initial diagnosis of Parkinson’s disease

Purpose Previous studies using dopamine transporter single-photon emission computed tomography (SPECT) to try and distinguish between patients with idiopathic Parkinsons disease (IPD) and patients with atypical parkinsonian syndromes (APS) have mainly focussed on patients with an already established clinical diagnosis of several years duration. Differences in the pattern of striatal involvement between IPD and APS have been found in only few studies. We hypothesized that distinguishing SPECT features might be most pronounced at an early disease stage, and the purpose of the present study was to investigate this hypothesis.Methods The study included 72 patients with an initial clinical diagnosis of IPD, supported by decreased striatal [¹²³I]-CIT binding on baseline SPECT. In ten patients, the diagnosis was changed to APS over a mean follow-up period of 62 months. We retrospectively compared the patterns of striatal involvement on the baseline SPECT scans between the group of patients (re)diagnosed with APS and the remaining 62 patients in whom a diagnosis of IPD was maintained.Results In the group of patients with APS, baseline [¹²³I]-CIT binding in both caudate nuclei was lower than in the group of patients with IPD. In addition, putamen to caudate binding ratios were higher in the group of APS patients. In spite of these differences, individual binding values showed considerable overlap between the groups.Conclusion [¹²³I]-CIT SPECT scanning in early-stage, untreated parkinsonian patients revealed a relative sparing of the caudate nucleus in patients with IPD as compared to patients later (re)diagnosed with APS. Nevertheless, the pattern of striatal involvement appears to have little predictive value for a later re-diagnosis of APS in individual cases.     

Enhancement of [123I]β-CIT binding in the striatum with clomipramine: Is there a serotonin-dopamine interaction?

Many reports support the concept of serotonergic-dopaminergic interaction in the brain. However, at present, there are few methods to study this relationship in vivo. The purpose of this study was to investigate the effect of serotonin (5-HT) uptake inhibitor, clomipramine, on a dopamine (DA) transporter ligand, [¹²³I]-CIT (RTI-55), in rat brain. Dose-dependent changes in [¹²³I]-CIT specific binding induced by clomipramine were studied in the striatum (rich in DA transporter) and the hypothalamus (rich in 5-HT transporter). The changes in the time-activity curves of [¹²³I]-CIT specific binding after clomipramine injection were also examined in these two regions. Using the cerebellum as the reference region,k ₃ andk ₄ values with and without clomipramine administration were estimated by a two-compartment kinetic analysis. Clomipramine inhibited [¹²³I]-CIT specific binding in the hypothalamus, but enhanced its specific binding in the striatum in a dose-dependent manner. Kinetic analysis showed thatk ₃ in the striatum was increased by 55%. In conclusion, enhancement of [¹²³I]-CIT binding in the striatum after clomipramine administration indicated the possibility of 5-HT-DA interaction.     

Relationship between striatal [123I]β-CIT binding and four major clinical signs in Parkinson’s disease

We investigated the correlation between clinical severity and striatal [123I]-CIT binding in 12 patients with Parkinson's Disease (PD: 6 men and 6 women, age: 65 +/- 7 years, Hoehn & Yahr stage: 1 to 3). The clinical severity of PD patients was measured with the Unified Parkinson's Disease Rating Scale (UPDRS) after withdrawal of antiparkinsonian medication at least 12 hours before assessment. [123I]beta-CIT binding in the caudate and putamen was measured at 3 hours [V'3 (day 1)], and at 24 hours [V'3 (day 2)) after tracer injection with small square ROIs. The specific striatal uptake index (day 2) was calculated with large square ROIs that encompassed the whole striatum. The best correlation (r = -0.82, p < 0.0012) was between putamenal V'3 (day 2) and the motor UPDRS scores. When the motor UPDRS scores were divided into four subscales, bradykinesia was the only sign that correlated significantly with putamenal V'3 (day 2) (r = -0.81, p < 0.002). [123I]beta-CIT SPECT is a useful marker of disease severity in PD with potential utility in the serial monitoring of disease progression.     

Do CSF levels of t-Tau,p-Tau and β1-42 amyloid correlate with dopaminergic system impairment in patients with a clinical diagnosis of Parkinson disease? A 123I-FP-CIT study in the early stages of the disease

Purpose

To investigate the relationships among cerebrospinal fluid (CSF) levels of t-Tau, p-Tau and Aβ_1-42 amyloid peptide and ¹²³I-FP-CIT uptake.

Methods

The study included 58 subjects (31 men and 27 women, age 67 ± 9 years) with a clinical diagnosis of Parkinson disease diagnosed according to the United Kingdom Parkinson Disease Society Brain Bank criteria. All subjects underwent a CSF assay 28 ± 3 days before ¹²³I-FP-CIT SPECT scanning. The relationships were evaluated by means of linear regression analysis and Pearson correlation.

Results

Striatal ¹²³I-FP-CIT was positively related to both t-Tau and p-Tau CSF values with low levels of t-Tau and p-Tau being related to a low uptake of ¹²³I-FP-CIT. In particular, differences with higher statistical significance were found for the striatum between the contralateral side and the side mainly affected on clinical examination (P?1-42 amyloid peptide and ¹²³I-FP-CIT binding.

Conclusion

The results of our study suggest that the presynaptic dopaminergic system is more involved in Parkinson disease patients with lower t-Tau and p-Tau CSF values while values of Aβ_1-42 amyloid peptide seems not to be related to nigrostriatal degeneration in our series.     

[123I]β-CIT single-photon emission tomography in Parkinson's disease reveals a smaller decline in dopamine transporters with age than in controls

In vivo studies using single-photon emission tomography (SPET) and positron emission tomography have shown an age-related decline in the number of striatal dopamine transporters in healthy subjects. We examined ten healthy subjects and 33 de novo patients with Parkinson's disease (PD) using [¹²³I]2-carbomethoxy-3-(4-iodophenyl)tropane ([¹²³I]-CIT) SPET. A clear age-related loss of dopamine transporters was found in the healthy subjects. In the PD group, controlling for the contribution of disease severity, we found a small (compared with controls) but significant decrease with aging, though only in the ipsilateral regions. This aging effect was especially pronounced in younger patients. We conclude that the use of age-correct SPET data in PD, based on studies with healthy subjects, may lead to an underor an overestimation of the striatal binding measures.     

Simple production of 77Br− and 123I− and their use in the labelling of [77Br]BrUdR and [123I]IUdR

Excitation functions for ⁷⁷Kr- and ¹²³Xe-production via the similar reactions Br(p,xn)⁷⁷Kr and¹²⁷I(p,5n)¹²³Xe, as well as their main radionuclide impurities (⁷⁶Kr, ⁷⁹Kr, ¹²¹Xe, ¹²²Xe, and ¹²⁵Xe), were studied in the proton energy ranges, 20–80 MeV (⁷⁷Kr) and 40–100 MeV (¹²³Xe). Thin targets (2–3 MeV) of NaBr and NaI were used and irradiated in the internal beam of the Uppsala synchrocyclotron. A simple technique of separating the radioactive gases from target was used. Optimal production conditions of ⁷⁷Br⁻ and ¹²³I⁻ were considered. A simple labelling technique of [⁷⁷Br]BrUdR and [¹²³I]IUdR is presented.     

Progression of dopaminergic degeneration in dementia with Lewy bodies and Parkinson’s disease with and without dementia assessed using 123I-FP-CIT SPECT

Purpose The objective of this study was to investigate the rate of progression of nigrostriatal dopaminergic loss in subjects with dementia with Lewy bodies (DLB), Parkinsons disease (PD) and PD with dementia (PDD) using serial ¹²³I-FP-CIT SPECT imaging. We hypothesised that striatal rates of decline in patients would be greater than in controls, and that DLB and PDD would show similar rates, reflecting the similarity in neurobiological mechanisms of dopaminergic loss between the two disorders.Methods We studied 20 patients with DLB, 20 with PD, 15 with PDD and 22 healthy age-matched controls. Semi-automated region of interest (ROI) analysis was performed on both baseline and repeat scans for each subject and mean striatal uptake ratios (caudate, anterior and posterior putamen) were calculated.Results Rates of decline in striatal binding between groups were assessed using ANCOVA. Significant differences between patients and controls were observed in caudate (DLB, PD, PDD, p0.01), anterior putamen (DLB, PDD, p0.05; PD, p=0.07) and posterior putamen (DLB, PD, PDD, p<0.006). Rates of decline were similar between DLB, PD and PDD.Conclusion In conclusion, this is the first study to show that significant progressive dopaminergic loss occurs in DLB and PDD using serial ¹²³I-FP-CIT SPECT. Dementia severity and motor impairment were correlated with decline, suggesting that dopaminergic loss may play an important role in cognitive as well as motor features.     

Brain perfusion scintigraphy with99mTc-HMPAO or99mTc-ECD and123I-β-CIT single-photon emission tomography in dementia of the Alzheimer-type and diffuse Lewy body disease

Dementia of the Alzheimer-type (DAT) is characterized by progressive cognitive decline, variably combined with frontal lobe release signs, parkinsonian symptoms and myoclonus. The features of diffuse Lewy body disease (DLBD), the second most common cause of degenerative dementia, include progressive cognitive deterioration, often associated with levodopa-responsive parkinsonism, fluctuations of cognitive and motor functions, psychotic symptoms (visual and auditory hallucinations, depression), hypersensitivity to neuroleptics and orthostatic hypotension. A recent report suggests that positron emission tomography studies in patients with degenerative dementia may be useful in the differential diagnosis of DAT and DLBD. However, the diagnostic role of single-photon emission tomography (SPET) studies remains to be established. The aim of this study was therefore to evaluate regional cerebral perfusion [with either technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) or^99mTc-ethyl cysteinate dimer (^99mTc-ECD) SPET] and striatal dopamine transporter density [using iodine-123 2-carboxymethoxy-3-[4-iodophenyl]tropane (¹²³I--CIT) SPET] in patients with DAT and DLBD. Six patients with probable DAT and seven patients with probable DLBD were studied. Blinded qualitative assessment by four independent raters of^99mTc-HMPAO or^99mTc-ECD SPET studies revealed bilateral temporal and/or parietal hypoperfusion in all DAT patients. There was additional frontal hypoperfusion in two patients and occipital hypoperfusion in one patient. In the DLBD group, regional cerebral perfusion had a different pattern. In addition to temporoparietal hypoperfusion there was occipital hypoperfusion resembling a horseshoe defect in six of seven patients. In the DAT group, the mean 3-h striatal/cerebellar ratio of¹²³I--CIT binding was 2.5±0.4, with an increase to 5.5±1.1 18 h after tracer injection. In comparison, in the DLBD patients the mean 3-h striatal/cerebellar ratio of¹²³I--CIT binding was significantly reduced to 1.7±0.3, with a modest increase to 2.1±0.4 18 h after tracer injection (P<0.05, Scheffe test, ANOVA). These results suggest that^99mTc-HMPAO or^99mTc-ECD and¹²³I--CIT SPET may contribute to the differential diagnosis between DAT and DLBD, showing different perfusion patterns and more severe impairment of dopamine transporter function in DLBD than in DAT.     

Progression of dopamine transporter decline in patients with the Parkinson variant of multiple system atrophy: a voxel-based analysis of [<Superscript>123</Superscript>I]β-CIT SPECT

Purpose  

We characterized the progression of dopamine transporter (DAT) decline in the striatum and extrastriatal regions including the midbrain and pons of patients with the Parkinson variant of multiple system atrophy (MSA-P) and compared longitudinally collected SPECT results with those in a cohort of patients with Parkinson's disease (PD).     

Topography of cerebral monoamine transporter availability in families with SCA2 mutations: a voxel-wise [123I]β-CIT SPECT analysis

Purpose The purpose of this study was to investigate the monoamine transporter status of dopamine, serotonin and norepinephrine throughout the brain in spinocerebellar ataxia type 2 (SCA2). To this end, nine patients were studied with [¹²³I]β-CIT SPECT. Methods Data were compared with ten age-matched healthy control subjects and ten patients with young-onset Parkinson’s disease (YOPD), matched for age. Parametric SPECT images of the specific-to-non-displaceable equilibrium partition coefficient (V ₃″), which is proportional to the receptor density (B _max), were generated. In order to objectively localise focal changes in β-CIT uptake throughout the brain volume without having to make an a priori hypothesis as to their location, statistical parametric mapping (SPM) was applied to SPECT images. Data clusters revealed by SPM, showing significant differences in V ₃″ values between groups, were transformed onto the individual V ₃″ image to obtain mean regional uptake values. Results Both SCA2 and YOPD patients showed significant decreases in striatal [¹²³I]β-CIT SPECT uptake when compared with controls. However, in SCA2 patients, additional reductions in caudate/anterior putamen, midbrain and pons [¹²³I]β-CIT uptake were localised with SPM. Conclusion Voxel-wise analysis of [¹²³I]β-CIT SPECT revealed more widespread decline of monoamine transporter availability in SCA2 than in YOPD, reflecting differences in the underlying pathology. We suggest that the quantification of midbrain and pons [¹²³I]β-CIT signal is likely to improve the diagnostic accuracy in patients presenting with clinical features of both SCA2 and YOPD at initial investigation.     

Evaluation of l-3-[123I]iodo-α-methyltyrosine SPET and [18F]fluorodeoxyglucose PET in the detection and grading of recurrences in patients pretreated for gliomas at follow-up: a comparative study with stereotactic biopsy

. Based on the results of stereotactic biopsy, we evaluated in a prospective fashion the efficiency of l-3-[¹²³I]iodo-α-methyltyrosine-single-photon emission tomography (SPET) and [¹⁸F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in the detection and grading of recurrences in patients previously treated for gliomas. The patient population comprised 30 individuals, nine with astrocytomas of grade II, ten with astrocytomas of grade IV, three with oligoastrocytomas of grade II, six with oligodendrogliomas of grade II and two with anaplastic oligodendrogliomas of grade III) suspected of recurrence and scheduled for further treatment. IMT SPET data were acquired using either by dual-or a triple-headed SPET camera, Multispect 2/3. FDG uptake was measured with an ECAT ART PET camera. Two independent observers classified PET and SPET images as positive or negative for tumour tissue. Uptake of FDG and IMT was evaluated visually and, in the case of IMT, also quantitatively by calculating the ratios between tracer accumulation in the lesion and the unaffected contralateral regions of reference using the region of interest (ROI) technique. The PET and SPET results were compared with the histopathological findings obtained either by stereotactic biopsy or in one case by open surgery. Glucose metabolism and amino acid uptake of recurrences of brain tumours as assessed by FDG-PET and IMT-SPET correlated highly with the histopathological findings. Based on the histopathological data, FDG-PET and IMT-SPET findings confirmed recurrence in all cases of high-grade gliomas (IV). A difference could be demonstrated in low-grade (II–III) tumour recurrences. True-positive IMT-SPET results were found in 86% of grade III and 75% of grade II recurrences, whereas FDG-PET yielded a sensitivity of 71% in tumours of grade III and 50% in those of grade II. With respect to the grade of malignancy of brain tumours at recurrence, IMT-SPET, in contrast to FDG-PET, does not permit adequate in vivo grading of non-mixed brain tumours of astrocytic or oligodendroglial origin. However, in this study FDG-PET did not permit discrimination between upgrading of low-grade oligoastrocytomas (II) into anaplastic oligodendrogliomas (III) and upgrading into glioblastomas (IV) The results of this study indicate that FDG-PET and IMT-SPET are equivalent to stereotactic biopsy in their ability to identify high-grade tumours at recurrence. IMT-SPET proved to be superior to FDG-PET in confirming low-grade recurrences. In the case of suspected progression of the grade of malignancy in ordinary gliomas, FDG-PET correlated significantly with the histopathological grading, whereas IMT-SPET did not. However, tumour grading by FDG-PET has a limitation in mixed brain tumours in that it is not possible to discriminate between progression of the oligo- versus the astrocytic tumour entity. In this case histopathological evaluation of the tumour grade remains necessary. Received 6 August and in revised form 2 November 1998     

Comparative value of brain perfusion SPECT and [123I]MIBG myocardial scintigraphy in distinguishing between dementia with Lewy bodies and Alzheimer’s disease

Purpose Both decreased occipital perfusion on brain single-photon emission computed tomography (SPECT) and reduction in cardiac ¹²³I-metaiodobenzylguanidine (MIBG) uptake are characteristic features of dementia with Lewy bodies (DLB), and potentially support the clinical diagnosis of DLB. The aim of this study was to compare the diagnostic value of these two methods for differentiation of DLB from Alzheimers disease (AD).Methods The study population comprised 19 patients with probable DLB and 39 patients with probable AD who underwent both SPECT with N-isopropyl-p-[¹²³I]iodoamphetamine and MIBG myocardial scintigraphy. Objective and quantitative measurement of perfusion in the medial occipital lobe, including the cuneus and lingual gyrus, was performed by the use of three-dimensional stereotactic surface projections.Results Medial occipital perfusion was significantly decreased in the DLB group compared with the AD group. The mean heart/mediastinum ratios of MIBG uptake were significantly lower in the DLB group than in the AD group. Although SPECT failed to demonstrate significant hypoperfusion in the medial occipital lobe in five patients with DLB, marked reduction of MIBG uptake was found in all patients with DLB. Receiver operating characteristic analysis revealed that MIBG myocardial scintigraphy enabled more accurate discrimination between DLB and AD than was possible with perfusion SPECT.Conclusion MIBG myocardial scintigraphy may improve the sensitivity in the detection of DLB. In particular, this method may provide a powerful differential diagnostic tool when it is difficult to distinguish cases of DLB from AD using brain perfusion SPECT.An editorial commentary on this paper is available at     

Does combined imaging of the pre- and postsynaptic dopaminergic system increase the diagnostic accuracy in the differential diagnosis of parkinsonism?

Purpose We hypothesized that combining pre- and postsynaptic quantitative information about the dopaminergic system would provide a higher diagnostic accuracy in the differential diagnosis of parkinsonism than specific striatal D₂ receptor binding alone. Therefore, the aim of the study was to introduce new semi-quantitative parameters and evaluate their ability to discriminate between Parkinson’s disease (IPS) and non-idiopathic parkinsonian syndromes (non-IPS). Methods In 100 patients (69 IPS, 31 non-IPS), postsynaptic [¹²³I]IBZM and presynaptic [¹²³I]FP-CIT SPECT scans were evaluated by observer-independent techniques. The diagnostic performances of striatal dopamine transporter (DAT) and D₂ receptor binding, their respective asymmetries, and a combination of pre- and postsynaptic asymmetry were evaluated with ROC analyses. A logistic regression model was generated combining factors to calculate the probability for each patient of belonging to either diagnostic group. Results D₂ receptor binding provided a sensitivity of 87.1% and a specificity of 72.5% with an area under the curve (AUC) of 0.866. The AUCs of other single parameters were lower than that of D₂ binding. A gain of diagnostic power (p = 0.026) was reached with a model combining pre- and postsynaptic asymmetries and D₂ binding (sensitivity 90.3%, specificity 73.9%, AUC 0.893). Conclusion The combination of quantitative parameters of presynaptic DAT and postsynaptic D₂ receptor binding demonstrates superior diagnostic power in the differentiation of patients with IPS and non-IPS than the established approach based on D₂ binding alone. Striatal D₂ receptor binding and the combination of DAT and IBZM binding asymmetries are the factors contributing most in separating these diagnostic groups.     

Serotonin transporter binding with [<Superscript>123</Superscript>I]β-CIT SPECT in major depressive disorder versus controls: effect of season and gender

Purpose  The serotonin system is undoubtedly involved in the pathogenesis of major depressive disorder (MDD). More specifically the serotonin transporter (SERT) serves as a major target for antidepressant drugs. There are conflicting results about SERT availability in depressed patients versus healthy controls. We aimed to measure SERT availability and study the effects of age, gender and season of scanning in MDD patients in comparison to healthy controls. Methods  We included 49 depressed outpatients (mean±SD 42.3 ± 8.3 years) with a Hamilton depression rating scale score above 18, who were drug-naive or drug-free for ≥4 weeks, and 49 healthy controls matched for age (±2 years) and sex. Subjects were scanned with single photon emission computed tomography (SPECT) using [¹²³I]β-CIT. SERT availability was expressed as specific to nonspecific binding ratios (BP_ND) in the midbrain and diencephalon with cerebellar binding as a reference. Results  In crude comparisons between patients and controls, we found no significant differences in midbrain or diencephalon SERT availability. In subgroup analyses, depressed males had numerically lower midbrain SERT availability than controls, whereas among women SERT availability was not different (significant diagnosis×gender interaction; p = 0.048). In the diencephalon we found a comparable diagnosis×gender interaction (p = 0.002) and an additional smoking×gender (p = 0.036) interaction. In the midbrain the season of scanning showed a significant main effect (p = 0.018) with higher SERT availability in winter. Conclusion  Differences in SERT availability in the midbrain and diencephalon in MDD patients compared with healthy subjects are affected by gender. The season of scanning is a covariate in the midbrain. The diagnosis×gender and gender×smoking interactions in SERT availability should be considered in future studies of the pathogenesis of MDD.     

Structural and neurochemical evaluation of the brain and pons in patients with Wilson’s disease

Purpose  

The aim of this study was to examine the structural-neurochemical abnormalities of the frontal white matter (FWM), deep gray matter nuclei, and pons in patients with Wilson’s disease (WD) using proton magnetic resonance spectroscopy (MRS) and diffusion-weighted imaging (DWI).