2024
PET imaging of M4 muscarinic acetylcholine receptors in rhesus macaques using [11C]MK-6884: Quantification with kinetic modeling and receptor occupancy by CVL-231 (emraclidine), a novel positive allosteric modulator
Belov V, Guehl N, Duvvuri S, Iredale P, Moon S, Dhaynaut M, Chakilam S, MacDonagh A, Rice P, Yokell D, Renger J, Fakhri G, Normandin M. PET imaging of M4 muscarinic acetylcholine receptors in rhesus macaques using [11C]MK-6884: Quantification with kinetic modeling and receptor occupancy by CVL-231 (emraclidine), a novel positive allosteric modulator. Cerebrovascular And Brain Metabolism Reviews 2024, 44: 1329-1342. PMID: 38477292, PMCID: PMC11342722, DOI: 10.1177/0271678x241238820.Peer-Reviewed Original ResearchConceptsPositive allosteric modulatorsReceptor occupancyNon-human primatesBinding potentialPositron emission tomographyMuscarinic acetylcholine receptorsAllosteric modulatorsNon-human primate brainM4 muscarinic acetylcholine receptorStriatal hyperdopaminergiaAcetylcholine receptorsBrain regionsCaudate nucleusTotal volume of distributionDose-dependent blockReference regionVolume of distributionPositron emission tomography imagingEmission tomographyReceptor levelsFunction of dosePET scansClinical trialsBlood-basedRhesus macaques
2021
Synthesis and Characterization of [18F]JNJ-46356479 as the First 18F-Labeled PET Imaging Ligand for Metabotropic Glutamate Receptor 2
Yuan G, Guehl N, Zheng B, Qu X, Moon S, Dhaynaut M, Shoup T, Afshar S, Kang H, Zhang Z, El Fakhri G, Normandin M, Brownell A. Synthesis and Characterization of [18F]JNJ-46356479 as the First 18F-Labeled PET Imaging Ligand for Metabotropic Glutamate Receptor 2. Molecular Imaging And Biology 2021, 23: 527-536. PMID: 33559035, PMCID: PMC8277681, DOI: 10.1007/s11307-021-01586-0.Peer-Reviewed Original ResearchConceptsNon-human primatesIn vivo PET imaging studiesNucleus accumbensGlutamate receptor 2PET imaging ligandsImaging ligandsParietal cortexBrain regionsPET imaging studiesPET radioligandIn vivo PET imaging experimentsVolume of distributionMGluR2C57BL/6 J micePET imaging experimentsPET studiesBrainSprague-Dawley ratsAlzheimer's diseaseBrain permeabilityPre-treatment studyImaging studiesDisordersRat studiesReversible kineticsRadiochemical Synthesis and Evaluation in Non-Human Primates of 3‑[11C]methoxy-4-aminopyridine: A Novel PET Tracer for Imaging Potassium Channels in the CNS
Guehl N, Neelamegam R, Zhou Y, Moon S, Dhaynaut M, Fakhri G, Normandin M, Brugarolas P. Radiochemical Synthesis and Evaluation in Non-Human Primates of 3‑[11C]methoxy-4-aminopyridine: A Novel PET Tracer for Imaging Potassium Channels in the CNS. ACS Chemical Neuroscience 2021, 12: 756-765. PMID: 33539063, PMCID: PMC8060895, DOI: 10.1021/acschemneuro.0c00791.Peer-Reviewed Original Research
2020
In-vivo Imaging of Mitochondrial Depolarization of Myocardium With Positron Emission Tomography and a Proton Gradient Uncoupler
Alpert N, Pelletier-Galarneau M, Kim S, Petibon Y, Sun T, Ramos-Torres K, Normandin M, Fakhri G. In-vivo Imaging of Mitochondrial Depolarization of Myocardium With Positron Emission Tomography and a Proton Gradient Uncoupler. Frontiers In Physiology 2020, 11: 491. PMID: 32499721, PMCID: PMC7243673, DOI: 10.3389/fphys.2020.00491.Peer-Reviewed Original ResearchMitochondrial membrane potentialPositron emission tomographyProton gradient uncouplerMembrane potentialIntracoronary infusionEmission tomographyPositron emission tomography scanBolus plus infusionVolume of distributionMitochondrial membraneCellular membrane potentialBAM15InfusionPreliminary dose-response experimentsMaximum depolarizationDose-response experimentsIn vivo imagingSecular equilibrium
2016
Pharmacokinetic Evaluation of the Tau PET Radiotracer 18F-T807 (18F-AV-1451) in Human Subjects
Wooten D, Guehl N, Verwer E, Shoup T, Yokell D, Zubcevik N, Vasdev N, Zafonte R, Johnson K, Fakhri G, Normandin M. Pharmacokinetic Evaluation of the Tau PET Radiotracer 18F-T807 (18F-AV-1451) in Human Subjects. Journal Of Nuclear Medicine 2016, 58: 484-491. PMID: 27660144, PMCID: PMC5334185, DOI: 10.2967/jnumed.115.170910.Peer-Reviewed Original ResearchConceptsDistribution volume ratioTraumatic brain injuryMetabolite-corrected arterial input functionPET imagingPlasma radioactivity concentrationsTemporal cortexDynamic PET imagesTotal volume of distributionVolume of distributionTraumatic brain injury subjectsMesial temporal cortexArterial blood samplesPosterior cingulate gyrusFocal uptakeSUV ratioHuman subjectsArterial input functionPosterior corpus callosumBolus injectionPharmacokinetic evaluation