Reduced cerebral DOPA uptake in adult patients suffering from phenylketonuria

Relationship between prefrontal cognitive functions and dopaminergic transmission: A [18F]-fluoro-l-DOPA PET study

Decreased dopamine D2/D3-receptor binding in temporal lobe epilepsy: an [18F]fallypride PET study.

Summary: Purpose: Although animal data are suggestive, evidence for an alteration of the extrastriatal dopaminergic system in human focal epilepsy is missing. Methods: To quantify D2/D3-receptor density, we studied seven patients with temporal lobe epilepsy (TLE) and nine agematched controls with positron emission tomography (PET) by using the high-affinity dopamine D2/D3-receptor ligand [ 18 F]Fallypride ([ 18 F]FP) suitable for imaging extrastriatal binding. TLE was defined by interictal and ictal video-EEG, magnetic resonance imaging (MRI), and [ 18 F]fluorodeoxyglucose ([ 18 F]FDG)-PET and was due to hippocampal sclerosis (HS), based on histology in all patients. Primary analysis was ba…

A comparative analysis of striatal and extrastriatal D2/D3 binding of five pharmacologically different “atypical” antipsychotics

The striatal and extrastriatal D2/D3 receptor-binding profile of clozapine in patients with schizophrenia.

Positron emission tomography (PET) studies reveal that clozapine at clinically used doses occupies less than 60% of D2/D3 dopamine receptors in human striatum. Here, the occupancy of D2/D3 dopamine receptors by clozapine in patients with schizophrenia was determined to test the hypothesis that clozapine binds preferentially to extrastriatal dopamine receptors. A total of 15 clozapine-treated inpatients with schizophrenia underwent a [18F]fallypride PET scan. Receptor occupancy was calculated as percent reduction in binding potential relative to unblocked values measured in seven normal volunteers. Mean D2/D3 receptor occupancy was statistically significantly higher in cortical (inferior tem…

Validating the DemTect with 18-Fluoro-2-Deoxy-Glucose Positron Emission Tomography as a Sensitive Neuropsychological Screening Test for Early Alzheimer Disease in Patients of a Memory Clinic

<i>Objectives:</i> The first study to validate the diagnostic value of the DemTect, a short neuropsychological screening test for dementia (8–10 min), using 18-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) in patients of a memory clinic. <i>Methods:</i> DemTect results were compared to the clinical diagnosis and to FDG-PET as a reference method for the early in vivo detection of Alzheimer’s disease (AD). <i>Results:</i> 38 patients (age 65.2 ± 9.8 years, 16 men, 22 women) were investigated using clinical standard examination, FDG-PET, and cranial magnetic resonance imaging. According to NINCDS-ADRDA and Petersen’s criteria, 18 patients had…

High opiate receptor binding potential in the human lateral pain system

To determine how opiate receptor distribution is co-localized with the distribution of nociceptive areas in the human brain, eleven male healthy volunteers underwent one PET scan with the subtype-nonselective opioidergic radioligand [(18)F]fluoroethyl-diprenorphine under resting conditions. The binding potential (BP), a parameter for the regional cerebral opioid receptor availability, was computed using the occipital cortex as reference region. The following regions of interest (ROIs) were defined on individual MR images: thalamus, sensory motor strip (SI/MI area), frontal operculum, parietal operculum, anterior insular cortex, posterior insular cortex, anterior cingulate cortex (ACC; peri-…

The unpleasantness of tonic pain is encoded by the insular cortex

Objective: Muscle pain differs from skin pain with respect to quality, accuracy of localization, and unpleasantness. This study was conducted to identify the brain regions associated with the affective-motivational component of tonic skin and muscle pain. Methods: Forty healthy volunteers were investigated in three groups with different F-18 fluorodeoxyglucose PET activation scans. A verbal rating scale (VRS) was used to quantify pain intensity and unpleasantness. One group was investigated during painful infusion of an acidified phosphate buffer (pH 5.2) into either muscle or skin for 30 minutes. Muscle and skin infusions were adjusted to achieve pain intensity rating of VRS = 40. The seco…

[ 18 F]Fluoroethylflumazenil: a novel tracer for PET imaging of human benzodiazepine receptors

5-(2'-[18F]Fluoroethyl)flumazenil ([18F]FEF) is a fluorine-18 labelled positron emission tomography (PET) tracer for central benzodiazepine receptors. Compared with the established [11C]flumazenil, it has the advantage of the longer half-life of the fluorine-18 label. After optimisation of its synthesis and determination of its in vitro receptor affinities, we performed first PET studies in humans. PET studies in seven healthy human volunteers were performed on a Siemens ECAT EXACT whole-body scanner after injection of 100-280 MBq [L8F]FEF. In two subjects, a second PET scan was conducted after pretreatment with unlabelled flumazenil (1 mg or 2.5 mg i.v., 3 min before tracer injection). A t…

Association of elevated phospho-tau levels with alzheimer-typical 18F-Fluoro-2-Deoxy-D-Glucose positron emission tomography findings in patients with mild cognitive impairment

Abstract Background Mild cognitive impairment is considered to be a transitional stage between normal aging and dementia. Phosphorylated tau protein in cerebrospinal fluid and even more decrements of cerebral glucose metabolism in parietal, temporal, or cingulate regions have shown favorable specificity for the diagnosis of Alzheimer dementia and could be useful supplementary tools to determine Alzheimer pathology in early stages. Methods We measured cerebrospinal fluid tau phosphorylated at threonine 181 protein, cerebrospinal fluid total tau, and cerebral glucose metabolism using 18F-fluoro-2-deoxy-D-glucose positron emission tomography in 16 patients with mild cognitive impairment and ag…

Cerebrospinal Fluid Tau Protein Levels and <sup>18</sup>F-Fluorodeoxyglucose Positron Emission Tomography in the Differential Diagnosis of Alzheimer’s Disease

<i>Aims:</i> In this study, we aimed to compare cerebrospinal fluid (CSF) levels of total tau (t-tau), phosphorylated tau (p-tau<sub>181</sub>) and positron emission tomography with <sup>18</sup>F-fluorodeoxyglucose (FDG-PET) in the differential diagnosis of Alzheimer’s disease (AD) under clinical conditions. <i>Method:</i> In a cross-sectional, blinded, single-center study, we examined a sample of 75 unselected memory clinic patients with clinical diagnoses of dementia of Alzheimer type (DAT; n = 24), amnestic mild cognitive impairment (MCI; n = 16), other dementias (n = 13) and nondemented controls (n = 22). Discriminative accuracy, sensitiv…

Asymmetry in dopamine D2/3 receptors of caudate nucleus is lost with age

Molecular and functional imaging techniques reveal evidence for lateralization of human cerebral function. Based on animal data, we hypothesized that asymmetry in dopamine neurotransmission declines during normal aging. In order to test this hypothesis, we measured dopamine D2/3 receptor availability with [18F]desmethoxyfallypride-PET (DMFP) in putamen and caudate nucleus (NC) of 21 healthy, right-handed males (24-60 years; 35+/-10). For volumetric analysis, high-resolution T1-weighted MR-images were obtained in 18 of the PET-subjects in order to assess possible age-related decreases in NC and putamen volume. The calculated DMFP binding potentials (BP) showed a right-ward asymmetry in NC of…

Observer independent analysis of cerebral glucose metabolism in patients with chronic fatigue syndrome.

Objectives: To evaluate cerebral glucose metabolism, assessed by 18-fluorodeoxyglucose positron emission tomography (FDG-PET), in patients with chronic fatigue syndrome (CFS), using an observer independent analytical approach; and to characterise any observed alterations by correlating them with neuropsychological deficits. Methods: 26 patients (13 female, 13 male) were examined. They all fulfilled the CDC diagnostic criteria for CFS. Their ages ranged from 26 to 61 years (mean (SD) age, 43 (9.3) years). They underwent extensive psychometric testing including the hospital anxiety and depression scale (HADS) and the short form 36 item health questionnaire (SF-36). Brain FDG-PET was done in a…

Net influx of plasma 6-[18F]fluoro-L-DOPA (FDOPA) to the ventral striatum correlates with prefrontal processing of affective stimuli.

Dopaminergic neurotransmission in the ventral and dorsal striatum interact with central processing of rewarding and reward-indicating stimuli, and may affect frontocortical-striatal-thalamic circuits regulating goal-directed behaviour. Thirteen healthy male volunteers were investigated with multimodal imaging, using the radioligand 6-[ 18 F]fluoro-L-DOPA (FDOPA) for positron emission tomography (PET) measurements of dopamine synthesis capacity, and also functional magnetic resonance imaging (fMRI) in a cognitive activation paradigm. We calculated the correlation between FDOPA net blood-brain influx (K app in ; ml/g/min) in the ventral and associative dorsal striatum and BOLD signal changes …

Modulation of [18F]fluorodopa (FDOPA) kinetics in the brain of healthy volunteers after acute haloperidol challenge.

In animal studies, acute antipsychotic treatment was shown to enhance striatal DOPA-decarboxylase (DDC) activity. However, this phenomenon has not been demonstrated in humans by positron emission tomography (PET). Therefore, we investigated acute haloperidol effects on DDC activity in humans using [18F]fluorodopa (FDOPA) PET. Nine healthy volunteers were scanned with FDOPA in drug-free baseline conditions and after 3 days of haloperidol treatment (5 mg/day). A continuous performance test (CPT) was administered in both conditions. The net blood-brain clearance of FDOPA (K(in)app) in striatum, mesencephalon, and medial prefrontal cortex was calculated by volume-of-interest analysis. The macro…

Reduced Cerebral Fluoro-l-Dopamine Uptake in Adult Patients Suffering from Phenylketonuria

Deficiency of phenylalanine hydroxylase activity in phenylketonuria (PKU) causes an excess of phenylalanine (Phe) throughout the body, predicting impaired synthesis of catecholamines in the brain. To test this hypothesis, we used positron emission tomography (PET) to measure the utilization of 6-[18F]fluoro-l-dopamine (FDOPA) in the brain of adult patients suffering from PKU and in healthy controls. Dynamic 2-h long FDOPA emission recordings were obtained in seven adult PKU patients (five females, two males; age: 21 to 27 years) with elevated serum Phe levels, but lacking neurologic deficits. Seven age-matched, healthy volunteers were imaged under identical conditions. The utilization of F…

A Knowledge-Based System for the Diagnosis of Alzheimer’s Disease

Therapies to slow down the progression of Alzheimer’s disease are most effective when applied in its initial stages. Therefore it is important to develop methods to diagnose the disease as early as possible. It is also desirable to establish standards which can be used generally by physicians who may not be experts in diagnosis of the disease. One possible method to obtain an early diagnosis is the evaluation of the glucose metabolism of the brain. In this paper we present a prototype of an expert system that automatically diagnoses Alzheimer’s disease on the basis of positron emission tomography images displaying the metabolic activity in the brain.

High striatal occupancy of D2-like dopamine receptors by amisulpride in the brain of patients with schizophrenia.

The 'atypicality' of the antipsychotic drug, amisulpride, has been attributed to preferential extrastriatal binding. Previous investigations of striatal D2 receptor occupancy by amisulpride revealed conflicting results. The aim of this PET study was to measure the striatal occupancy by amisulpride and to correlate it with the corresponding drug plasma concentrations. Nine amisulpride-treated patients and 12 healthy volunteers serving as controls were studied with PET and [18F]desmethoxyfallypride. Occupancy values and plasma concentrations were nonlinearly fitted to an E max model. Results showed 43-85% (putamen) and 67-90% (caudate) D2-like receptor occupancy. Plasma amisulpride concentrat…

Acute Alcohol Effects on Neuronal and Attentional Processing: Striatal Reward System and Inhibitory Sensory Interactions under Acute Ethanol Challenge

The acute influence of ethanol on cerebral activity induces complex psycho-physiological effects that are considerably more pronounced during acute ethanol influx than during maximal blood alcohol concentration (elimination phase). Despite the psychiatric and forensic relevance of these different ethanol effects, the underlying neuronal mechanisms are still unclear. In total, 20 male healthy volunteers were investigated each with three different experimental conditions in a randomized order using an intravenous ethanol challenge (40 g bolus infusion): during influx phase, elimination phase, and under placebo condition. During and after the ethanol (or placebo) infusion, neuropsychological t…

High opiate receptor binding potential in the human lateral pain system: A (FEDPN)PET study

Baseline [18F]-FDOPA kinetics are predictive of haloperidol-induced changes in dopamine turnover and cognitive performance: A positron emission tomography study in healthy subjects.

The telencephalic dopamine innervations contribute to the modulation of cognitive processing. However, the relationship between cognitive effects of D(2/3)-receptor antagonism and dopamine transmission is not described in healthy subjects. We therefore tested effects of acute haloperidol (5 mg/d over 3 days) on continuous performance task (CPT) performance and 6-[(18)F]-fluoro-l-DOPA (FDOPA) PET parameters. Nine physically and mentally healthy male men performed two FDOPA-PET scans including arterial plasma withdrawal. Over 3 days before the second scan, all subjects were treated with 5 mg/d haloperidol orally. Using our novel steady-state analysis, we calculated the intrinsic rate of the c…

Corrigendum to “The thalamus as the generator and modulator of EEG alpha rhythm: A combined PET/EEG study with lorazepam challenge in humans” [NeuroImage 22 (2004) 637–644]

Department of Psychiatry, Johannes Gutenberg–University Mainz, 55131 Mainz, GermanyAvailable online 2 May 20061053-8119/$ - see front matter D 2006 Elsevier Inc. All rights reserved.doi:10.1016/j.neuroimage.2006.03.007DOI of original article:10.1016/j.neuroimage.2004.01.047.* Corresponding author. Department of Nuclear Medicine, Johannes Gutenberg–University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany. Fax: +496131 17 2448.E-mail address: schreckenberger@nuklear.klinik.uni-mainz.de (M. Schreckenberger).Available online on ScienceDirect (www.sciencedirect.com).

18F-labeling of peptides by means of an organosilicon-based fluoride acceptor.

Fluorine-18 is among the most commonly used radionuclides for positron emission tomography (PET). This non-invasive imaging technique is capable of providing in vivo information about the distribution of radiolabeled biomolecules by 1808 coincidence detection of two simultaneously emitted photons from positron–electron annihilation. Although a number of different radiotracers have been successfully employed in PET, only a few, such as 2-[F]fluoro-2-deoxy-d-glucose (FDG) and [F]fluorodopa, have gained widespread application in nuclear medicine. The reason for this is that the regioselective introduction of F into tracer molecules is often non-specific and radiochemical yields (RCY) of the Fl…

'Prefrontal' cognitive performance of healthy subjects positively correlates with cerebral FDOPA influx: an exploratory [18F]-fluoro-L-DOPA-PET investigation.

Dopamine neurotransmission influences those cognitive processes, which are generally regarded as prefrontal cortical functions. In previous positron‐emission‐tomography (PET) studies, net blood‐brain clearance of [(18)F]‐fluoro‐l‐DOPA (FDOPA) correlated with impaired cognitive performance in patients with Parkinson's disease or schizophrenia. We hypothesized that FDOPA influx also correlates with performance of cognitive tasks associated with prefrontal functioning in healthy volunteers. The net blood‐brain clearance of FDOPA (K [Formula: see text]) was mapped in a group of 11 healthy volunteers and calculated in striatal volumes‐of‐interest. The Wisconsin‐Card‐Sorting‐Test (WCST), Stroop‐T…

18F-Markierung von Peptiden mithilfe eines Organosilicium-Fluoridacceptors