P. Landais

The relation of putamen and caudate nucleus 18F-Dopa uptake to motor and cognitive performances in Parkinson’s disease

The contribution of striatal (caudate nucleus-putamen) dopaminergic deficiency to the severity of motor signs is well established in Parkinsons disease (PD), while its role in the occurrence of cognitive and mood changes remains unresolved. We therefore measured in 27 non-demented PD patients and 10 age-matched controls striatal uptake of [18F]-6-fluoro-L-Dopa (F-Dopa) with PET, and mood (Beck depression), memory (Grober-Buschke), frontal executive functions (verbal fluency and Wisconsin card sorting), and attentional processing of sensory stimuli (N2-P3 auditory event-related potentials--ERPs). Locomotor disability of patients was assessed by Hoehn and Yahr score and Unified Parkinsons Disease Rating Scale (UPDRS). ANOVA showed that memory, but neither frontal lobe functions nor ERPs, was significantly altered in PD patients, whereas indices of depression were found only in advanced PD. The F-Dopa rate constant Ki was significantly reduced in the striatum, more in putamen than caudate nucleus, and inversely correlated with disease duration. A significant inverse correlation was found between both putamen and caudate nucleus Ki and Hoehn and Yahr score, and between putamen--but not caudate nucleus Ki --and UPDRS motor score. Principal components analysis (PCA) of PD patients Ki values and mood, cognitive and ERP parameters gave a three-factor solution. Variables contributing to factor 1 were memory score and N2-P3 ERP latencies, those to factor 2 were striatal Ki values, and those to factor 3 frontal executive performances. Depression did not segregate with any variable. Our findings suggest that unlike locomotor disability, cognitive abilities and mood state of non-demented PD patients are for the most part unrelated to striatal dopaminergic depletion and may result from dysfunction of extra-striatal dopaminergic or from non-dopaminergic systems.

Effects of GABAA receptors activation on brain glucose metabolism in normal subjects and temporal lobe epilepsy (TLE) patients. A positron emission tomography (PET) study Part I: Brain glucose metabolism is increased after GABAA receptors activation

Though gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the human central nervous system, the metabolic response to GABA system activation remains imperfectly known. We studied in vivo with positron emission tomography (PET) the variations of glucose metabolism in the human brain after stimulation of the GABAA receptors by systemic administration of the specific GABAA agonist, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP). These investigations were performed in three normal volunteers and as part of presurgical evaluation for temporal lobe epilepsy in six patients. While clinical and electroencephalographic (EEG) monitoring showed a sedative effect and sleepiness after THIP administration, glucose metabolism was paradoxically increased in grey matter structures, which are known to have a high density of GABAA receptors. These findings suggest that the pharmacological activation of GABA pathways, although inhibitory and producing a decrease of vigilance, increases the energetic demand at least during a phase of GABA agonist action, probably at the synaptic or at the glial cell level.

Effects of GABAA receptors activation on brain glucose metabolism in normal subjects and temporal lobe epilepsy (TLE) patients. A positron emission tomography (PET) study Part II: The focal hypometabolism is reactive to GABAA agonist administration in TLE

Positron emission tomography (PET) using [18F]fluorodeoxyglucose (FDG) was used to study the metabolic response of focal hypometabolism to the administration of a specific GABAA agonist (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol), THIP, in six temporal lobe epilepsy (TLE) patients. After THIP injection, the increase of glucose metabolism in the hypometabolic focus was larger than the mean increase reported in the whole brain (Part I; Epilepsy Res., 19 (1994) 45-54). Within the hypometabolic focus, this increase was significantly higher in regions with the lowest basal metabolic level. This metabolic response in the hypometabolic focus, observed in the absence of any epileptic discharge during FDG accumulation and PET data acquisition, suggests that GABAA receptors are up-regulated or, at least, preserved in TLE.

Fluorination of aromatic compounds from 1-aryl-3,3-dimethyltriazenes and fluoride anions in acidic medium: 2. Synthesis of (S)-[18F]-3-fluoro-α-methylphenylalanine

Abstract We propose here a new methodology to prepare 3-fluoro-α-methylphenylalanine in which fluorine is introduced at the end of the synthesis, on an elaborated substrate bearing a triazeno substituent which is decomposed by triflic acid in the presence of fluoride anions (yield=31% versus 19 F − ). As 18 F − cannot be available free of other basic anions, this technique has been modified and adapted with some success to the radiosynthesis of [ 18 F ]-3-fluoro-α-methylphenylalanine.

Identification of 2-chloro-2-deoxyglucose (2-CIDG) and d-glucose as impurities formed in the synthesis of 2-18F]Fluoro-2-deoxyglucose (2-18FDG)

Abstract 2-Chloro-2-0deoxyglucose (2-CIDG) and d -glucose were identified in formulated 2-[ 18 F]fluoro-2-deoxyglucose (2- 18 FDG) by gas chromatographic analyses (GC) and gas chromatography coupled to mass spectrometer (GC/MS), as impurities formed during radiosynthesis. The impurities were most likely produced from the mannose triflate precursor in presence of an aqueous solution of HCl.

Factor analysis of dynamic structures (FADS) for quantitative modelling of positron emission tomographic (PET) image sequences

Summary form only given, as follows. From positron emission tomography (PET) image sequences it is possible to estimate biological parameters by means of measurements inside regions of interest. Several compartments, with various contributions, are present in each region. FADS automatically provides factors (kinetics corresponding to a pure compartment), factor images (spatial distribution of the factor), and their respective contributions. Using three radioisotopes with different decay time constants to simulate biological kinetics, mixed in various proportions in several vials, the authors validated FADS for (1) the number of kinetics and the expected time constants, (2) the spatial distribution of the compartments, and (3) the percentage of isotopes in each vial.<<ETX>>

Evaluation of fractional errors in pixels and regions in a time of flight PET scanner

The coefficient of variation (standard deviation over mean: s/m) was computed in regions of interest (ROIs) and compared to the value obtained in pixels in a time of flight PET scanner. Using a homogeneous cylindrical phantom, the authors collected events in list mode and reconstructed a dynamic series of 256*256 images for 0.5, 1, 2, 5, 10 and 50 (*106) events per image. Circular ROIs with the same and increasing sizes were drawn at different positions in the field of view. Using Hanning (cosine) filtered images, the s/m varied between 76 and 8.3% (103 and 14%) for pixels while it was at most 7.5% (9.2%) for ROIs. The s/m values were higher in the direct plane (DP) than in the cross plane (CP) due to its higher sensitivity. Two-way analysis of variance showed no ROI position effect in DP or CP separately but a significant count/pixel effect. s/m for pixels and for ROIs were linearly correlated to the expected noise to signal ratio calculated according to a published model. For ROI studies, cosine filtered images demonstrated a 22% higher s/m than Hanning filtered images.