Jobert A

References (5)

Title : Quantitative measurement of cerebral acetylcholinesterase using - Blomqvist_2001_J.Cereb.Blood.Flow.Metab_21_114
Author(s) : Blomqvist G , Tavitian B , Pappata S , Crouzel C , Jobert A , Doignon I , Di Giamberardino L
Ref : Journal of Cerebral Blood Flow & Metabolism , 21 :114 , 2001
Abstract : [11C]physostigmine, an acetylcholinesterase inhibitor, has been shown to be a promising positron emission tomography ligand to quantify the cerebral concentration of the enzyme in animals and humans in vivo. Here, a quantitative and noninvasive method to measure the regional acetylcholinesterase concentration in the brain is presented. The method is based on the observation that the ratio between regions rich in acetylcholinesterase and white matter, a region almost entirely deprived of this enzyme, was found to become approximately constant after 20 to 30 minutes, suggesting that at late time points the uptake mainly contains information about the distribution volume. Taking the white matter as the reference region, a simplified reference tissue model, with effectively one reversible tissue compartment and three parameters, was found to give a good description of the data in baboons. One of these parameters, the ratio between the total distribution volumes in the target and reference regions, showed a satisfactory correlation with the acetylcholinesterase concentration measured postmortem in two baboon brains. Eight healthy male subjects were also analyzed and the regional enzyme concentrations obtained again showed a good correlation with the known acetylcholinesterase concentrations measured in postmortem studies of human brain.
ESTHER : Blomqvist_2001_J.Cereb.Blood.Flow.Metab_21_114
PubMedSearch : Blomqvist_2001_J.Cereb.Blood.Flow.Metab_21_114
PubMedID: 11176277

Title : In vivo PET study of cerebral [11C] methyl- tetrahydroaminoacridine distribution and kinetics in healthy human subjects - Traykov_1999_Eur.J.Neurol_6_273
Author(s) : Traykov L , Tavitian B , Jobert A , Boller F , Forette F , Crouzel C , Di Giamberardino L , Pappata S
Ref : Eur Journal of Neurology , 6 :273 , 1999
Abstract : It is unclear whether the palliative effects of tetrahydroaminoacridine (THA) (tacrine, Cognex) on the clinical symptoms of patients affected by Alzheimer's disease (AD) are the result of its inhibitory activity on acetylcholinesterase or on other complex sites of action. In order to investigate the cerebral distribution and kinetics of THA in the human brain in vivo, we performed positron emission tomography (PET) imaging with [11C]N-methyl-tetrahydro-aminoacridine (MTHA) in healthy human volunteers. After intravenous injection, [11C]MTHA crossed the blood-brain barrier and reached its maximum uptake between 10 and 40 minutes, depending on the brain regions. Uptake was higher in the grey matter structures, and lower in the white matter. After this peak, the radioactivity remained quasi- constant until 60 minutes in all regions with a half-life varying from 2.44 hours in the thalamus to 3.42 hours in the cerebral cortex. The ratios of regional to whole cerebral cortex brain radioactivity calculated between 50 and 70 minutes after the tracer injection were 1.14 +/- 0.04, 1.07 +/- 0. 03 and 1.06 +/- 0.04 in the putamen, cerebellum and thalamus, respectively. Overall, these results show that: (1) [11C]MTHA crosses the blood-brain barrier easily and is highly concentrated in the brain; (2) the regional brain distribution of [11C]MTHA does not parallel that of in vivo acetylcholinesterase (AChE) concentrations; and (3) the cerebral kinetics of [11C]MTHA are consistent with known plasmatic pharmacokinetics of THA in AD patients. We conclude that PET imaging with [11C]MTHA is a useful method for assessing the cerebral distribution and kinetics of THA in vivo.
ESTHER : Traykov_1999_Eur.J.Neurol_6_273
PubMedSearch : Traykov_1999_Eur.J.Neurol_6_273
PubMedID: 10210906

Title : In vivo imaging of human cerebral acetylcholinesterase - Pappata_1996_J.Neurochem_67_876
Author(s) : Pappata S , Tavitian B , Traykov L , Jobert A , Dalger A , Mangin JF , Crouzel C , Di Giamberardino L
Ref : Journal of Neurochemistry , 67 :876 , 1996
Abstract : We report here the first positron emission tomography (PET) images showing the in vivo regional distribution of acetylcholinesterase (AChE) in human brain. The study was carried out in eight healthy human volunteers using as a tracer [11C]-physostigmine ([11C]PHY), an inhibitor of AChE. After intravenous injection of [11C]PHY, radioactivity was rapidly taken up in brain tissue and reached maximal uptake within a few minutes, following a regional pattern mostly related to cerebral perfusion. After the peak, the cerebral radioactivity gradually decreased with a half-life varying from 20 to 35 min, depending on the brain structure. [11C] PHY retention was higher in regions rich in AChE, such as the striatum (half-life, 35 min), than in regions poor in AChE, such as the cerebral cortex (half-life, 20 min). At later times (25-35 min postinjection), the cerebral distribution of [11C]PHY was typical of AChE activity: putamen-caudate > cerebellum > brainstem > thalamus > cerebral cortex, with a striatal to cortex ratio of 2. These results suggest that PET studies with [11C]PHY can provide in vivo brain mapping of human AChE and are promising for the study of changes in AChE levels associated with neurodegenerative diseases.
ESTHER : Pappata_1996_J.Neurochem_67_876
PubMedSearch : Pappata_1996_J.Neurochem_67_876
PubMedID: 8764619

Title : Positron emission tomography study of [11C]methyl-tetrahydroaminoacridine (methyl-tacrine) in baboon brain - Tavitian_1993_Eur.J.Pharmacol_236_229
Author(s) : Tavitian B , Pappata S , Bonnot-Lours S , Prenant C , Jobert A , Crouzel C , Di Giamberardino L
Ref : European Journal of Pharmacology , 236 :229 , 1993
Abstract : THA (1,2,3,4-tetrahydro-9-amino-acridine, tacrine), a potential therapeutic agent for patients suffering from Alzheimer's disease, has multiple pharmacological sites of action in the brain. In order to study the cerebral binding sites of THA in vivo, we labeled a close derivative of THA with carbon 11 for positron emission tomography (PET) analysis. We report the biodistribution of this compound, 1,2,3,4-tetrahydro-9-[11C]methylaminoacridine ([11C]MTHA), in the rodent and describe the first PET experiments in non-human primates. The distribution of [11C]MTHA in baboon brain, although rather diffuse in the gray matter, showed a higher concentration in the cortex and basal ganglia than in the cerebellum and binding could be displaced (50%) by cold THA. These results suggest that [11C]MTHA is a promising PET ligand for the study of the cerebral binding of THA.
ESTHER : Tavitian_1993_Eur.J.Pharmacol_236_229
PubMedSearch : Tavitian_1993_Eur.J.Pharmacol_236_229
PubMedID: 8319751

Title : In vivo visualization of acetylcholinesterase with positron emission tomography - Tavitian_1993_Neuroreport_4_535
Author(s) : Tavitian B , Pappata S , Planas AM , Jobert A , Bonnot-Lours S , Crouzel C , Di Giamberardino L
Ref : Neuroreport , 4 :535 , 1993
Abstract : The cerebral distribution of [11C]physostigmine, an acetylcholinesterase inhibitor, was studied with autoradiography in rats and positron emission tomography in primates. In rat brain [11C]physostigmine radioactivity was exactly superimposable to acetylcholinesterase activity, being highest in the basal ganglia, moderate in the cortex and hippocampus, and low in the cerebellum. In primate brain, the early blood-flow dependent distribution of [11C]physostigmine was followed by a rapid redistribution to acetylcholinesterase-rich regions such as the striatum. The cerebral uptake of [11C]physostigmine was significantly reduced by competition with an excess of unlabeled physostigmine. These results suggest that [11C]physostigmine is a promising new ligand for in vivo imaging of acetylcholinesterase activity with PET.
ESTHER : Tavitian_1993_Neuroreport_4_535
PubMedSearch : Tavitian_1993_Neuroreport_4_535
PubMedID: 8513134