A5083583275- Neuroscience and Neuropharmacology Research
- Drug Transport and Resistance Mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurotransmitter Receptor Influence on Behavior
- Medical Imaging Techniques and Applications
- Nicotinic Acetylcholine Receptors Study
- Pharmacological Effects and Toxicity Studies
- Receptor Mechanisms and Signaling
- Parkinson's Disease Mechanisms and Treatments
- Epilepsy research and treatment
- Glioma Diagnosis and Treatment
- Tryptophan and brain disorders
- Pain Mechanisms and Treatments
- Neuropeptides and Animal Physiology
- Anesthesia and Neurotoxicity Research
- Ion channel regulation and function
- Radiopharmaceutical Chemistry and Applications
- Pharmacogenetics and Drug Metabolism
- Cancer Treatment and Pharmacology
- Nanoparticles: synthesis and applications
- Heavy metals in environment
- Cardiac Ischemia and Reperfusion
- Metabolism and Genetic Disorders
- Neurological disorders and treatments
- Ion Transport and Channel Regulation
Centre National de la Recherche Scientifique
2015-2025
CEA Paris-Saclay
2016-2025
Inserm
2016-2025
Université Paris-Saclay
2016-2025
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2015-2025
Institut d'Imagerie Biomédicale
2011-2025
Laboratoire d’Imagerie Biomédicale
2021-2025
Frédéric Joliot Institute for Life Sciences
2020
Université Paris-Sud
2015-2019
Institut Galien Paris-Saclay
2019
Nicotinic acetylcholine receptors (nAChRs) are involved in a familial form of frontal lobe epilepsy, autosomal dominant nocturnal epilepsy (ADNFLE). In several ADNFLE families, mutations were identified the nAChR α4 or β2 subunit, which together compose main cerebral nAChR. Electrophysiological assessment using vitro expression systems indicated gain function mutant receptors. However precise mechanisms by they contribute to pathogenesis focal remain obscure, especially since α4β2 nAChRs...
[(11)C]SL-25.1188 [(S)-5-methoxymethyl-3-[6-(4,4,4-trifluorobutoxy)-benzo[d]isoxazol-3-yl]-oxazolidin-2-one], an oxazolidinone derivative, was characterized in baboons as a radioligand for the vivo visualization of MAO-B using positron emission tomography (PET). After i.v. injection, [(11)C]SL25.1188 presented rapid phase distribution blood (about 5 min), followed by T(1/2) elimination 85 +/- 14 min. Plasma metabolism analysis showed that is stable at least 30 Brain uptake with highest one...
[<sup>18</sup>F]DPA-714 [<i>N,N</i>-diethyl-2-(2-(4-(2[<sup>18</sup>F]-fluoroethoxy)phenyl)5,7dimethylpyrazolo[1,5a]pyrimidin-3-yl)acetamide] is a new radioligand currently used for imaging the 18-kDa translocator protein in animal models of neuroinflammation and recently humans. The biodistribution by positron emission tomography (PET) baboons vitro vivo metabolism were investigated rats, baboons, Whole-body PET experiments showed high uptake radioactivity kidneys, heart, liver,...
Abstract Notwithstanding potential neurotoxicity of inhaled titanium dioxide nanoparticles (TiO 2 NPs), the toxicokinetics and consequences on blood-brain barrier (BBB) function remain poorly characterized. To improve risk assessment, we need to evaluate impact BBB under realistic environmental conditions take into account vulnerability status such as age. 12–13 week 19-month-old male rats were exposed by inhalation 10 mg/m 3 TiO nano-aerosol (6 hrs/day, 5 day/week, for 4 weeks). We showed...
In this preclinical pilot study, we used [11C]UCB-J PET imaging to monitor the synaptic modulation in depression and after fluoxetine. was performed a validated mouse model of depression/anxiety (CORT model), effect 5-week treatment with fluoxetine tested. Depression/anxiety phenotype antidepressant action were confirmed using novelty-suppressed feeding test, previously CORT model. data showed significant decreases volume distribution (VT) most brain regions mice compared controls 5 weeks...
Abstract Within a novel series of 2‐oxazolidinones developed in the past by Sanofi‐Synthélabo, SL25.1188 (( S )‐5‐methoxymethyl‐3‐[6‐(4,4,4‐trifluorobutoxy)benzo[ d ]isoxazol‐3‐yl]oxazolidin‐2‐one), compound that inhibits selectively and competitively MAO‐B human rat brain (Ki values 2.9 8.5 nM for MAO‐B, respectively, ED 50 (rat) : 0.6 mg/kg p.o.), was considered an appropriate candidate imaging this enzyme with positron emission tomography. labelled carbon‐11 ( T 1/2 20.38 min) one...
<h3>Abstract</h3> Time implicitly shapes cognition, but time is also explicitly represented, for instance in the form of durations. Parsimoniously, brain could use same mechanisms implicit and explicit timing. Yet, evidence has been equivocal, revealing both joint versus separate signatures Here, we directly compared timing using magnetoencephalography, whose temporal resolution allows investigating different stages processes. Implicit predictability was induced an auditory paradigm by a...
Abstract The effects of acute alcohol exposure to the central nervous system are hypothesized involve innate immune system. neuroimmune response an initial and was investigated using translocator protein 18 kDa (TSPO) PET imaging, a non‐invasive marker glial activation, in adolescent baboons. Three different alcohol‐naive baboons (3–4 years old, 9 14 kg) underwent F‐DPA‐714 experiments before, during 7–12 months after this (0.7–1.0 g/l). brain distribution ( V T ; ml/cm 3 ) estimated several...
The quantitative relationship between the disruption of blood-brain barrier (BBB) and recruitment glial cells was explored in a mouse model endotoxemia. [ 18 F]2-Fluoro-2-deoxy-sorbitol ([ F]FDS) PET imaging used as paracellular marker for monitoring BBB permeability after i.v injection increasing doses lipopolysaccharide (LPS) or vehicle (saline, n = 5). brain distribution F]FDS ( V T , mL.cm −3 ) estimated using kinetic modeling. LPS dose-dependently increased 4 mg/kg (5.2 ± 2.4-fold, 4, p...
In the aim to develop an efficient fluorinated probe for positron emission tomography (PET) exploration of dopamine transporter (DAT), we studied several in vitro and vivo characteristics phenyltropane derivative (<i>E</i>)-<i>N</i>-(4-fluorobut-2-enyl)-2β-carbomethoxy-3β-(4′-tolyl)nortropane (LBT-999). on rat striatal membrane, [<sup>3</sup>H]LBT-999 bound a single site with <i>K</i><sub>d</sub> 9 nM, <i>B</i><sub>max</sub> 17 pmol/mg protein, very high selectivity DAT [IC<sub>50</sub>...
LBT-999 (8-((E)-4-fluoro-but-2-enyl)-3β-p-tolyl-8-aza-bicyclo[3.2.1]octane-2β-carboxylic acid methyl ester) is a cocaine derivative belonging to new generation of highly selective dopamine transporter ligands (KD:9 nM). was labelled with fluorine-18 at its fluoromethylvinyl moiety using the following two-step radiochemical process: (a) No-carrier-added nucleophilic aliphatic radiofluorination from (E)-1, 4-ditosyloxybut-2-ene and activated K[18F]F-Kryptofix®222 complex in acetonitrile 70°C...
The neuroinflammatory response to morphine exposure modulates its antinociceptive effects, tolerance, and dependence. Positron emission tomography radioligands for translocator protein-18kDa such as [18F]DPA-714 are noninvasive biomarkers of glial activation, a hallmark neuroinflammation.[18F]DPA-714 positron imaging was performed in 5 baboons at baseline 2 hours after i.m. injection (1 mg/kg). Brain kinetics metabolite-corrected input function were measured estimate brain...
Only partial deficiency/inhibition of P-glycoprotein (P-gp, ABCB1) function at the blood-brain barrier (BBB) is likely to occur in pathophysiological situations or drug-drug interactions. This raises questions regarding sensitivity available PET imaging probes detect moderate changes P-gp living BBB. In vitro, half-maximum inhibitory concentration (IC 50 ) potent inhibitor tariquidar P-gp-overexpressing cells was significantly different using either [ 11 C]verapamil (44 nM), C]...
Domperidone and metoclopramide are widely prescribed antiemetic drugs with distinct neurological side effects. The impact of P-glycoprotein (P-gp)-mediated efflux at the blood−brain barrier (BBB) on brain exposure BBB permeation was compared in vitro vivo using positron emission tomography (PET) imaging rats radiolabeled analogs [11C]domperidone [11C]metoclopramide. In P-gp-overexpressing cells, IC50 tariquidar, a potent P-gp inhibitor, drastically different (221 nM [198−248 nM]) or...
Abstract LBT‐999 (8‐(( E )‐4‐fluoro‐but‐2‐enyl)‐3‐beta‐ p ‐tolyl‐8‐aza‐bicyclo[3.2.1]octane‐2‐beta‐carboxylicacid methyl ester) is a recently developed cocaine derivative belonging to new generation of highly selective dopamine transporter (DAT) ligands ( K D : 9 nM for the DAT and IC 50 > 1000 serotonin norepinephrine transporter). Initial fluorine‐18‐labelling was based on robust reliable two‐step radiochemical pathway often reported such tropane derivatives, involving first preparation...
[(11)C]befloxatone is a high-affinity, reversible, and selective radioligand for the in vivo visualization of monoamine oxidase A (MAO-A) binding sites using positron emission tomography (PET). The multi-injection approach was used to study baboons interactions between MAO-A [(11)C]befloxatone. model included four compartments seven parameters. arterial plasma concentration, corrected metabolites, as input function. experimental protocol-three injections labeled and/or unlabeled...
Abstract A new tropane derivative, ( E )‐ N ‐(4‐fluorobut‐2‐enyl)‐2β‐carbomethoxy‐3β‐(4′‐tolyl)nortropane (LBT‐999), was evaluated in baboons as a carbon‐11 radioligand for studies of the dopamine transporter (DAT) using positron emission tomography (PET). Brain uptake high striatum (17 and 13% ID/100 mL tissue putamen caudate, respectively), moderate midbrain thalamus (5 3% tissue, low cortex cerebellum (2% tissue) at 30 min post injection. The striatum‐to‐cerebellum ratio (30 110...