Susanne Asenbaum

SPECT imaging of dopamine and serotonin transporters with [123I]β-CIT. Binding kinetics in the human brain

Single photon emission computerized tomography (SPECT) studies in non-human primates have previously shown that the cocaine derivative [123I]-2-β-carbomethoxy-3-β-(4-iodophenyl)-tropane ([123I]β-CIT) labels dopamine transporters in the striatum and serotonin transporters in the hypothalamusmidbrain area. Here, we report on the regional kinetic uptake of [123I]β-CIT in the brain of 4 normal volunteers and 2 patients with Parkinsons disease. In healthy subjects striatal activity increased slowly to reach peak values at about 20 hours post injection. In the hypothalamus-midbrain area peak activities were observed at about 4 hours with a slow decrease thereafter. Low activity was observed in cortical and cerebellar areas. The striatal to cerebellar ratio was about 4 after 5 hours and 9 after 20 hours. In 2 patients with idiopathic Parkinsons disease striatal activity was markedly decreased while the activity in hypothalamus-midbrain areas was only mildly diminished. Uptake into cortical and cerebellar areas appeared to be unchanged in Parkinsons disease. Consequently, in Parkinsons disease the striatal to cerebellar ratio was decreased to values around 2.5 after 20 hours. These preliminary methodological studies suggest that [123I]β-CIT is a useful SPECT ligand for studying dopamine and possibly also serotonin transporters in the living human brain.

EANM procedure guidelines for PET brain imaging using [ 18 F]FDG, version 2

These guidelines summarize the current views of the European Association of Nuclear Medicine Neuroimaging Committee (ENC). The purpose of the guidelines is to assist nuclear medicine practitioners in making recommendations, performing, interpreting, and reporting the results of fluorine-18 fluoro-2-deoxyglucose ([18F]FDG) PET imaging of the brain. The aim is to help achieve a high standard of FDG imaging, which will increase the diagnostic impact of this technique in neurological and psychiatric practice. The present document replaces a former version of the guidelines that were published in 2002 [1] and includes an update in the light of advances in PET technology, the introduction of hybrid PET/CT systems and the broadening clinical indications for FDG brain imaging. These guidelines are intended to present information specifically adapted for European practice. The information provided should be taken in the context of local conditions and regulations.

Progression of dopaminergic degeneration in Parkinson's disease and atypical parkinsonism: A longitudinal β-CIT SPECT study

Atypical parkinsonian syndromes (APS) such as multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration are characterized by poor response to antiparkinsonian medication and rapid clinical deterioration. We used SPECT and [123I]β‐CIT as a label of dopamine transporters to study the progression of presynaptic dopaminergic degeneration in Parkinsons disease (PD) and APS. Twenty‐four PD patients with short disease duration (2.4 ± 1.5 years), 12 PD patients with long disease duration (9.2 ± 2.6 years), 10 patients with APS (disease duration 2.1 ± 1.5 years), and nine patients with essential tremor (ET) underwent sequential [123I]β‐CIT SPECT imaging with an interval of 25.5 ± 10.3 (13–63) months. The age‐related decline of striatal β‐CIT binding was studied cross‐sectionally in 30 healthy subjects. The ratio of striatum/cerebellum −1 at 20 hours after tracer injection, reflecting specific‐to‐nondisplaceable binding, was used as the primary SPECT outcome measure. At scan 1, striatal β‐CIT binding was reduced in PD patients with short disease duration (−42% compared with age‐corrected normal values) and long disease duration (−51%), and APS (−36%), but normal in ET. During the observation period striatal β‐CIT binding significantly declined in patients with APS (14.9% per year) and short duration PD (7.1% per year), whereas PD patients with long disease duration and patients with ET showed no significant change of striatal β‐CIT binding between scans 1 and 2. The relative annual reduction from age‐corrected normal values at the time of scan 1 was significantly higher in patients with APS than in PD patients with short disease duration (9.6 vs. 4.3%, P = 0.004). These results demonstrate a rapid decline of striatal β‐CIT binding in patients with atypical parkinsonian syndromes, exceeding the reduction in PD. The dopaminergic degeneration in PD appears to slow down during the course of the disease. SPECT with [123I]β‐CIT is a sensitive marker of disease progression in parkinsonian disorders.

[123I]β-CIT spect in multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration

Differentiation between Parkinsons disease (PD) and other neurodegenerative disorders with parkinsonian features, such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), is difficult on clinical grounds. We studied the pattern of dopaminergic degeneration in 18 patients with probable MSA, 8 patients with PSP, 4 patients with CBD, 48 patients with PD and a similar degree of disability, and 14 control subjects performing single photon emission computed tomography (SPECT) 20 hours after injection of [123I]β‐CIT. Overall striatal binding was significantly reduced in MSA (−51% of normal mean), PSP (−60%), CBD (−35%), and PD (−58%), without overlap with control values. Asymmetry of striatal β‐CIT binding was significantly increased in patients with CBD and PD, as compared with control subjects. Although asymmetry seemed to be less pronounced in MSA and PSP than in PD, this was not statistically significant. Putamen–caudate nucleus ratios in patients with PD, MSA, and PSP, but not with CBD, were significantly reduced, as compared with control subjects. In conclusion, [123I]β‐CIT SPECT reliably enables the visualization of the presynaptic dopaminergic lesion in patients with MSA, PSP, and CBD. In most patients, however, it does not seem to be possible to differentiate these disorders from PD with this method.

[123I]-β-CIT SPECT imaging shows reduced brain serotonin transporter availability in drug-free depressed patients with seasonal affective disorder

Abstract Background: Numerous findings indicate alterations in brain serotonin systems in seasonal affective disorder (SAD). [ 123 I]-2-β-carbomethoxy-3-β-(4-iodophenyl)-tropane ([ 123 I]-β-CIT) labels serotonin transporters (5-HTTs) in the midbrain. We performed a [ 123 I]-β-CIT single photon emission computer tomography (SPECT) study under the hypothesis of lower [ 123 I]-β-CIT binding reflecting reduced central 5-HTT availability in depressed SAD patients. Methods: Depressed SAD patients and healthy control subjects were investigated using [ 123 I]-β-CIT SPECT 4 hours and again 24 hours after tracer injection. Subjects had either never used psychotropic medication or had been drug-free for at least 6 months prior to the investigation. Specific-to-nondisplaceable partition coefficient (V 3 ′′) was calculated for the thalamus-hypothalamus and the midbrain-pons; the cerebellum served as a reference region. Results: Patients showed a reduction in V 3 ′′ in thalamus-hypothalamus (2.41 ± 0.3 vs. 2.84 ± 0.4; p = .026) 24 hours post tracer injection (p.i.). No difference between patients and control subjects was found in midbrain-pons (1.31 ± 0.2 vs. 1.42 ± 0.2; p = .39). No differences were detected in the SPECT acquisitions 4 hours p.i. Conclusions: Depressed SAD patients showed lower specific-to-nondisplaceable [ 123 I]-β-CIT binding in the region of interest (ROI) thalamus-hypothalamus. The small size of the midbrain-pons ROI may have contributed to the failure to show a difference in this ROI as well. Similar to reduced midbrain 5-HTT availability in nonseasonal depression, depression in SAD seems to be associated with reduced 5-HTT availability to the thalamus-hypothalamus.

[123I]β-CIT and SPECT in essential tremor and Parkinson's disease

Summary. Resting and postural tremor may occur in essential tremor (ET) and Parkinsons disease (PD). The aim of the present study was to investigate the cocaine derivative [123I]β-CIT, which labels striatal dopamine transporters, and SPECT in differentiating these diseases. Methods: 30 healthy volunteers, 32 patients with ET and 29 patients with idiopathic PD of Hoehn/Yahr stage I were investigated. Specific over nondisplaceable binding ratios (target/cerebellum-1) were calculated for the striatum, the caudate nucleus and the putamen separately as well as a ratio putamen/caudate and the percent deviation of each patients ratio from age-expected control values. Results: Striatal [123I]β-CIT binding ratios in ET were within normal ranges and showed only a discrete elevation to age-expected control values (+14.6%). In PD significantly reduced specific binding was evident not only contralaterally to the clinically affected side (putamen: −62%, caudate nucleus: −35%), but also ipsilaterally (putamen: −45%, caudate nucleus: −22%). All investigated parameters differed significantly between PD and controls and ET respectively. Conclusion: Imaging striatal dopamine transporters with [123I]β-CIT and SPECT could clearly distinguish between ET and PD in an early stage of the disease. Findings do not suggest a subclinical involvement of dopaminergic nigrostriatal neurons in ET.

beta-CIT SPECT demonstrates blockade of 5HT-uptake sites by citalopram in the human brain in vivo.

The cocaine analogue 2-β-carbomethoxy-3-β-(4-iodophenyl)-tropane (β-CIT) is a potent ligand for both dopamine- and serotonin uptake sites which in its123I labeled form can be used for single photon emission computerized tomography (SPECT). It was demonstrated previously by SPECT-studies in non-human primates that123I-β-CIT binds to dopamine transporters in the striatum and to serotonin transporters in hypothalamus and midbrain. The aim of the present study was to compare123I-β-CIT binding in the brain stem of normal controls and a group of subjects under treatment with the selective serotonin reuptake inhibitor (SSRI) citalopram.123I-β-CIT- SPECT was performed in 12 depressed patients under 20 mg (n=5), 40 mg (n=6) and 60 mg (n=1) citalopram daily, in one untreated depressed patient and in 11 controls at regular time intervals up till 24 hours p.inj. A highly significant reduction of β-CIT binding was found in an area including mesial thalamus, hypothalamus, midbrain and pons in patients under citalopram compared to controls (44.1 ± 14.4 vs. 82.3 ± 18.6 cpms/mCi × kg body weight; specific binding 4 hrs p.inj.; p=0.0001). No differences were seen between the high and low dose group and no changes were found in the striatum.123I-β-CIT binding in the brain stem and striatum in one untreated depressed patient fell within the range of control values. To our knowledge this is the first report directly demonstrating the effect of a selective serotonin uptake inhibitor in the brain in humans in vivo. SPECT measurements of serotonin uptake sites in patients with depression and other psychiatric disorders might provide better insights into the pathophysiology of these disorders and into mechanisms of drug action.

No evidence for in vivo regulation of midbrain serotonin transporter availability by serotonin transporter promoter gene polymorphism

BACKGROUND A polymorphism in the serotonin transporter promoter gene region (5-HTTLPR) has been shown to influence the quantity of serotonin transporter expressed in human cell lines: the 5-HTTLPR short allele (s) has been associated with reduced 5-HTT expression when compared to cells carrying the 5-HTTLPR long allele (l). We performed a single photon emission computed tomography (SPECT) study using the ligand [(123)I]-2-beta-carbomethoxy-3-beta-(4-iodophenyl)tropane ([(123)I]-beta-CIT) to measure 5-HTT availability in 16 healthy subjects genotyped for 5-HTTLPR. METHODS SPECT scans were performed 24 hours after tracer injection, regions of interest anatomically corresponding to the thalamus-hypothalamus and mesencephalon-pons areas were compared to the binding in the cerebellum, representing the nondisplaceable [(123)I]-beta-CIT-binding (results expressed as target activity minus cerebellum activity/cerebellum activity). DNA from peripheral nuclear blood cells was genotyped for 5-HTTLPR using standard polymerase chain reaction methods. RESULTS Specific binding ratios in the thalamus-hypothalamus were 2.65 +/- 0.4 in subjects with the l/l genotype (n = 3), 2.76 +/- 0.5 in subjects with the l/s genotype (n = 9), and 2.77 +/- 0.4 in subjects with the s/s genotype (n = 4). Binding ratios in the mesencephalon-pons were 1.43 +/- 0.3 (l/l; n = 3), 1.37 +/- 0.3 (l/s; n = 9), and 1.28 +/- 0.3 (s/s; n = 4). None of these differences was statistically significant. CONCLUSIONS Our data provide no evidence for in vivo functional regulation of 5-HTT availability by 5-HTTLPR in the thalamus-hypothalamus and mesencephalon-pons of healthy subjects.

5-Aminolevulinic acid is a promising marker for detection of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement.

Because of intratumoral heterogeneity, diffusely infiltrating gliomas that lack significant contrast enhancement on magnetic resonance imaging are prone to tissue sampling error. Subsequent histologic undergrading may delay adjuvant treatments. 5‐Aminolevulinic acid (5‐ALA) leads to accumulation of fluorescent porphyrins in malignant glioma tissue, and is currently used for resection of malignant gliomas. The aim of this study was to clarify whether 5‐ALA might serve as marker for visualization of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement for precise intraoperative tissue sampling.

[123I]beta-CIT SPECT distinguishes vascular parkinsonism from Parkinson's disease.

We investigated whether [123I]‐β‐CIT and single‐photon emission computed tomography (SPECT) imaging distinguishes patients with clinically suspected vascular parkinsonism (VP) from patients with idiopathic Parkinsons disease (PD). [123I]β‐CIT SPECT is a sensitive marker of dopaminergic degeneration, and the degree of striatal binding reduction in PD correlates with disease severity. Thirteen patients who fulfilled rigid clinical criteria for VP (mean ± S.D.: age, 76.5 ± 5.3 years; disease duration, 3.6 ± 2.8 years), 20 PD patients (age, 66.2 ± 9.5 years; disease duration, 4.3 ± 2.7 years), and 30 healthy persons (age, 44.6 ± 19.2 years) underwent [123I]β‐CIT SPECT imaging. Age‐corrected striatal β‐CIT binding was reduced on average by 40.8% in PD but was near normal in the VP group (mean reduction, 1.2%). This difference was statistically significant (Z = 4.68; P < 0.001). The left–right asymmetry of striatal β‐CIT binding was significantly increased in the PD group compared with normal controls and the VP group (F(2) = 17.4, P <0.001). Moreover, putamen–caudate nucleus ratios were significantly reduced in PD compared with both VP patients and healthy controls (F(2) = 65.5, P < 0.001). Whole striatal β‐CIT binding was more than one standard deviation above the mean PD values in all but one of the individual VP patients. Our findings suggest that the presynaptic dopaminergic deficits seen in PD are absent in most patients with VP. [123I]β‐CIT SPECT imaging may be useful to help distinguish between PD and VP patients during life.