Publications by authors named "Nicolas Tournier"

Duchenne muscular dystrophy (DMD) is associated with a range of cognitive and behavioral problems. Brain-related comorbidities show clinical heterogeneity depending on the position of the mutation within the multi-promoter dystrophin (DMD) gene, likely due to the differential impact of mutations on the expression of distinct brain dystrophins. A deficiency of the full-length brain dystrophin, Dp427, has been associated with enhanced stress reactivity, characterized by abnormal fear responses in both patients and mdx mouse model.

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Objectives: Resective surgery in drug-resistant focal epilepsy (DRFE) requires extensive evaluation to localize the epileptogenic zone (EZ). When non-invasive phase 1 assessments (electroencephalography, EEG; magnetic resonance imaging, MRI; and F-Fluorodeoxyglucose-positron emission tomography, [F]FDG-PET) are inconclusive for EZ localization, invasive investigations such as stereo-EEG (SEEG) are necessary. Epileptogenicity maps (Ems) visualize the EZ using SEEG-identified ictal high-frequency oscillations (iHFOs).

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Creatine transporter deficiency (CTD) is an inborn error of creatine (Cr) metabolism in which Cr is not properly distributed to the brain due to a mutation in the Cr transporter (CrT) SLC6A8 gene. CTD is associated with developmental delays and with neurological disability in children. Dodecyl creatine ester (DCE), as a Cr prodrug, is a promising drug to treat CTD after administration by the nasal route, taking advantage of the nose-to-brain pathway.

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Background: P-glycoprotein (P-gp) is an efflux transporter which is abundantly expressed at the blood-brain barrier (BBB) and which has been implicated in the pathophysiology of various brain diseases. The radiolabelled antiemetic drug [C]metoclopramide is a P-gp substrate for positron emission tomography (PET) imaging of P-gp function at the BBB. To assess whether [C]metoclopramide can detect increased P-gp function in the human brain, we employed drug-resistant temporal lobe epilepsy (TLE) as a model disease with a well characterised, regional P-gp up-regulation at the BBB.

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Article Synopsis
  • Regadenoson is a drug that temporarily disrupts the blood-brain barrier (BBB) and was studied using PET imaging in rats for its effectiveness in delivering drugs to the brain.
  • In the study, regadenoson notably increased the penetration of a small molecule and a nanoparticle into the brain, with a peak effect observed in the striatum region.
  • The study found that while regadenoson improved delivery for certain compounds, it had no significant effect on larger monoclonal antibodies, highlighting both the benefits and limitations of using regadenoson for brain drug delivery.
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Neuroimaging biomarkers are needed to investigate the impact of smoking withdrawal on brain function. NFL-101 is a denicotinized aqueous extract of tobacco leaves currently investigated as an immune-based smoking cessation therapy in humans. However, the immune response to NFL-101 and its ability to induce significant changes in brain function remain to be demonstrated.

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Numerous studies suggest that blood-brain barrier (BBB) dysfunction may contribute to the progression of Alzheimer's disease (AD). Clinically available neuroimaging methods are needed for quantitative "scoring" of BBB permeability in AD patients. [F]2-fluoro-2-deoxy-sorbitol ([F]FDS), which can be easily obtained from simple chemical reduction of commercial [F]2-fluoro-2-deoxy-glucose ([F]FDG), was investigated as a small-molecule marker of BBB permeability, in a pre-clinical model of AD using in vivo PET imaging.

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We will be serving as the Guest Editor for this very interesting Special Issue on "Non-Invasive Device-Mediated Drug Delivery to the Brain Across the Blood-Brain Barrier" [...

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The quantitative relationship between the disruption of the blood-brain barrier (BBB) and the recruitment of glial cells was explored in a mouse model of endotoxemia. [F]2-Fluoro-2-deoxy-sorbitol ([F]FDS) PET imaging was used as a paracellular marker for quantitative monitoring of BBB permeability after i.v injection of increasing doses of lipopolysaccharide (LPS) or vehicle (saline, n = 5).

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P-glycoprotein (P-gp, encoded in humans by the gene and in rodents by the genes) is a membrane transporter that can restrict the intestinal absorption and tissue distribution of many drugs and may also contribute to renal and hepatobiliary drug excretion. The aim of this study was to compare the performance and sensitivity of currently available radiolabeled P-gp substrates for positron emission tomography (PET) with the single-photon emission computed tomography (SPECT) radiotracer [Tc]Tc-sestamibi for measuring the P-gp function in the kidneys and liver. Wild-type, heterozygous (), and homozygous () knockout mice were used as models of different P-gp abundance in excretory organs.

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Among opioids, buprenorphine presents a favorable safety profile with a limited risk of respiratory depression. However, fatalities have been reported when buprenorphine is combined to a benzodiazepine. Potentiation of buprenorphine interaction with opioid receptors (ORs) with benzodiazepines, and/or vice versa, is hypothesized to explain this drug-drug interaction (DDI).

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Article Synopsis
  • Drugs work better and can have side effects based on how much of them gets into the tissues in our body.
  • Scientists use special cells to study how drugs move in and out of tissues because they can't get real tissue samples easily.
  • They found a way to predict how drugs like glyburide and pitavastatin behave in the liver using their new method, and it worked well with their studies!
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The passage of antibodies through the blood-brain barrier (BBB) and the blood-tumoral barrier (BTB) is determinant not only to increase the immune checkpoint inhibitors efficacy but also to monitor prognostic and predictive biomarkers such as the programmed death ligand 1 (PD-L1) via immunoPET. Although the involvement of neonatal Fc receptor (FcRn) in antibody distribution has been demonstrated, its function at the BBB remains controversial, while it is unknown at the BTB. In this context, we assessed FcRn's role by pharmacokinetic immunoPET imaging combined with focused ultrasounds (FUS) using unmodified and FcRn low-affinity IgGs targeting PD-L1 in a preclinical orthotopic glioblastoma model.

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P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are two ATP-binding cassette efflux transporters that are coexpressed at the human blood-brain barrier (BBB) and blood-retina barrier (BRB). While pharmacological inhibition of P-gp and/or BCRP results in increased brain distribution of dual P-gp/BCRP substrate drugs, such as the tyrosine kinase inhibitor erlotinib, the effect of P-gp and/or BCRP inhibition on the retinal distribution of such drugs has hardly been investigated. In this study, we used positron emission tomography (PET) imaging to assess the effect of transporter inhibition on the distribution of [C]erlotinib to the human retina and brain.

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Purpose: PET imaging using [C]metoclopramide revealed the importance of P-glycoprotein (P-gp, ABCB1) in mediating the brain-to-blood efflux of substrates across the blood-brain barrier (BBB). In this work, the elimination rate constant from the brain (k), calculated from dynamic PET images without the need for arterial blood sampling, was evaluated as an outcome parameter for the interpretation of [C]metoclopramide PET data.

Procedures: k parameter was obtained by linear regression of log-transformed brain time-activity curves (TACs).

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Background And Objectives: Translocator protein 18 kDa (TSPO) PET imaging is used to monitor glial activation. Recent studies have proposed TSPO PET as a marker of the epileptogenic zone (EZ) in drug-resistant focal epilepsy (DRFE). This study aims to assess the contributions of TSPO imaging using [F]DPA-714 PET and [F]FDG PET for localizing the EZ during presurgical assessment of DRFE, when phase 1 presurgical assessment does not provide enough information.

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The efflux transporter P-glycoprotein (P-gp) at the blood-brain barrier limits the cerebral uptake of various xenobiotics. To assess the sensitivity of [C]metoclopramide to measure decreased cerebral P-gp function, we performed [C]metoclopramide PET scans without (baseline) and with partial P-gp inhibition by tariquidar in wild-type, heterozygous and homozygous mice as models with controlled levels of cerebral P-gp expression. Brains were collected to quantify P-gp expression with immunohistochemistry.

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The P-glycoprotein (P-gp/ABCB1) is a major efflux transporter which impedes the brain delivery of many drugs across the blood-brain barrier (BBB). Focused ultrasound with microbubbles (FUS) enables BBB disruption, which immediate and delayed impact on P-gp function remains unclear. Positron emission tomography (PET) imaging using the radiolabeled substrate [C]metoclopramide provides a sensitive and translational method to study P-gp function at the living BBB.

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The need for carbon-labeled radiotracers is increasingly higher in drug discovery and development (carbon-14, β, = 5730 years) as well as in positron emission tomography (PET) for in vivo molecular imaging applications (carbon-11, β, = 20.4 min). However, the structural diversity of radiotracers is still systematically driven by the narrow available labeled sources and methodologies.

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Aim: Buprenorphine mainly acts as an agonist of mu-opioid receptors (mu-OR). High dose buprenorphine does not cause respiratory depression and can be safely administered to elicit typical opioid effects and explore pharmacodynamics. Acute buprenorphine, associated with functional and quantitative neuroimaging, may therefore provide a fully translational pharmacological challenge to explore the variability of response to opioids .

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In the lungs, the membrane transporter P-glycoprotein (P-gp) is expressed in the apical (i.e. lumen-facing) membrane of airway epithelial cells and in the luminal (blood-facing) membrane of pulmonary capillary endothelial cells.

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[11C]metoclopramide PET imaging provides a sensitive and translational tool to explore P-glycoprotein (P-gp) function at the blood-brain barrier (BBB). Patients with neurological diseases are often treated with cytochrome (CYP) modulators which may impact the plasma and brain kinetics of [11C]metoclopramide. The impact of the CYP inducer carbamazepine or the CYP inhibitor ritonavir on the brain and plasma kinetics of [11C]metoclopramide was investigated in rats.

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