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
2022
Radiochemical Synthesis and Evaluation of 3‑[11C]Methyl-4-aminopyridine in Rodents and Nonhuman Primates for Imaging Potassium Channels in the CNS
Sun Y, Guehl N, Zhou Y, Takahashi K, Belov V, Dhaynaut M, Moon S, Fakhri G, Normandin M, Brugarolas P. Radiochemical Synthesis and Evaluation of 3‑[11C]Methyl-4-aminopyridine in Rodents and Nonhuman Primates for Imaging Potassium Channels in the CNS. ACS Chemical Neuroscience 2022, 13: 3342-3351. PMID: 36417797, PMCID: PMC9732819, DOI: 10.1021/acschemneuro.2c00364.Peer-Reviewed Original ResearchConceptsRegional brain time-activity curvesBrain time-activity curvesOne-tissue compartment modelBlood-brain barrierConsistent with <i>inNonhuman primatesTime-activity curvesPositron emission tomographySpinal cord injuryDemyelinated neuronsNeurological symptomsPotassium channelsNeuronal conductionBrain uptakeEmission tomographyStille cross-couplingMultiple sclerosisCord injurySlow kineticsBrain permeabilityTraumatic brainMyelin sheathStronger binding affinityNeuronsBrainPET imaging studies to investigate functional expression of mGluR2 using [11C]mG2P001
Yuan G, Dhaynaut M, Guehl N, Neelamegam R, Moon S, Qu X, Poutiainen P, Afshar S, Fakhri G, Normandin M, Brownell A. PET imaging studies to investigate functional expression of mGluR2 using [11C]mG2P001. Cerebrovascular And Brain Metabolism Reviews 2022, 43: 296-308. PMID: 36172629, PMCID: PMC9903221, DOI: 10.1177/0271678x221130387.Peer-Reviewed Original ResearchConceptsPositive allosteric modulatorsPositron emission tomographyNon-human primatesMGluR2 positive allosteric modulatorPositron emission tomography imagingPositive allosteric modulator of mGluR2Metabotropic glutamate receptor 2Positron emission tomography imaging studiesExpression of mGluR2Glutamate receptor 2MGluR2 functionPsychiatric disordersMGluR2 expressionTissue glutamate concentrationMGluR2Expressing mGluR2Allosteric modulatorsRat brainTransfected CHO cellsReceptor 2Glutamate concentrationEmission tomographyImaging studiesPharmacological effectsImaging ligandsDesign, Synthesis, and Characterization of [18F]mG2P026 as a High-Contrast PET Imaging Ligand for Metabotropic Glutamate Receptor 2
Yuan G, Dhaynaut M, Guehl N, Afshar S, Huynh D, Moon S, Iyengar S, Jain M, Pickett J, Kang H, Ondrechen M, Fakhri G, Normandin M, Brownell A. Design, Synthesis, and Characterization of [18F]mG2P026 as a High-Contrast PET Imaging Ligand for Metabotropic Glutamate Receptor 2. Journal Of Medicinal Chemistry 2022, 65: 9939-9954. PMID: 35802702, PMCID: PMC9434700, DOI: 10.1021/acs.jmedchem.2c00593.Peer-Reviewed Original ResearchConceptsPositive allosteric modulatorsMetabotropic glutamate receptor 2Glutamate receptor 2Cu-mediated radiofluorinationPET imaging ligandsReceptor 2High molar activityExcellent radiochemical purityGloSensor assayPositron emission tomography radiotracersClasses of positive allosteric modulatorsNon-human primatesJNJ-46356479Radiochemical yieldBrain heterogeneityAllosteric modulatorsBrain uptakeMGluR2Molar activityLigandBrainBrain permeabilityImaging ligandsBinding kineticsMetabotropicPET imaging of mitochondrial function in acute doxorubicin-induced cardiotoxicity: a proof-of-principle study
Detmer F, Alpert N, Moon S, Dhaynaut M, Guerrero J, Guehl N, Xing F, Brugarolas P, Shoup T, Normandin M, Pelletier-Galarneau M, El Fakhri G, Petibon Y. PET imaging of mitochondrial function in acute doxorubicin-induced cardiotoxicity: a proof-of-principle study. Scientific Reports 2022, 12: 6122. PMID: 35414642, PMCID: PMC9005533, DOI: 10.1038/s41598-022-10004-6.Peer-Reviewed Original ResearchConceptsLeft anterior descending coronary arteryDoxorubicin-induced cardiotoxicityCardiac membrane potentialDoxorubicin infusionMembrane potentialAnimal modelsAcute doxorubicin-induced cardiotoxicityLeft anterior descending coronary artery territoryAcute cardiotoxic effectsAnterior descending coronary arteryControl saline infusionDescending coronary arteryDoxorubicin doseSaline infusionTest infusionCardiotoxic effectsMitochondrial membrane potentialInfusion catheterCoronary arteryInfusionMitochondrial functionDoxorubicinMyocardial areaPET imagingIntracoronary catheterImpact of 40 Hz Transcranial Alternating Current Stimulation on Cerebral Tau Burden in Patients with Alzheimer’s Disease: A Case Series1
Dhaynaut M, Sprugnoli G, Cappon D, Macone J, Sanchez J, Normandin M, Guehl N, Koch G, Paciorek R, Connor A, Press D, Johnson K, Pascual-Leone A, Fakhri G, Santarnecchi E. Impact of 40 Hz Transcranial Alternating Current Stimulation on Cerebral Tau Burden in Patients with Alzheimer’s Disease: A Case Series1. Journal Of Alzheimer's Disease 2022, 85: 1667-1676. PMID: 34958021, PMCID: PMC9023125, DOI: 10.3233/jad-215072.Peer-Reviewed Original ResearchConceptsMicroglia activationGamma spectral powerDecrease of microglia activationNo adverse eventsTranscranial alternating current stimulationSlow disease progressionPlacebo-controlled conditionsPreclinical dataCase seriesAdverse eventsGamma oscillationsElectrophysiological assessmentP-tauMouse modelDisease progressionMesial regionMild to moderate ADAnimal modelsPatientsPET imagingAlzheimer's diseaseSpectral powerAD mouse modelAD patientsProtein clearanceSynthesis and Characterization of 5‑(2-Fluoro-4‑[11C]methoxyphenyl)-2,2-dimethyl-3,4-dihydro‑2H‑pyrano[2,3‑b]pyridine-7-carboxamide as a PET Imaging Ligand for Metabotropic Glutamate Receptor 2
Yuan G, Dhaynaut M, Lan Y, Guehl N, Huynh D, Iyengar S, Afshar S, Jain M, Pickett J, Kang H, Wang H, Moon S, Ondrechen M, Wang C, Shoup T, Fakhri G, Normandin M, Brownell A. Synthesis and Characterization of 5‑(2-Fluoro-4‑[11C]methoxyphenyl)-2,2-dimethyl-3,4-dihydro‑2H‑pyrano[2,3‑b]pyridine-7-carboxamide as a PET Imaging Ligand for Metabotropic Glutamate Receptor 2. Journal Of Medicinal Chemistry 2022, 65: 2593-2609. PMID: 35089713, PMCID: PMC9434702, DOI: 10.1021/acs.jmedchem.1c02004.Peer-Reviewed Original ResearchConceptsNegative allosteric modulatorsMetabotropic glutamate receptor 2Positron emission tomographyGlutamate receptor 2MGluR2 functionNeuropsychiatric disordersDrug effectsBrain heterogeneityReceptor 2Allosteric modulatorsMGluR2Nonhuman primatesBrain imagingPositron emission tomography imagingPositron emission tomography imaging ligandsHigh molar activityEmission tomographyExcellent radiochemical purityImaging ligandsBlocking agentsPET imagingMolar activityTherapeutic targetMetabotropicDisorders
2021
Evaluation of Fluorinated Cromolyn Derivatives as Potential Therapeutics for Alzheimer’s Disease
Shoup T, Griciuc A, Normandin M, Quinti L, Walsh L, Dhaynaut M, Moon S, Guehl N, Brugarolas P, Elmaleh D, Fakhri G, Tanzi R. Evaluation of Fluorinated Cromolyn Derivatives as Potential Therapeutics for Alzheimer’s Disease. Journal Of Alzheimer's Disease 2021, 80: 775-786. PMID: 33579853, DOI: 10.3233/jad-201419.Peer-Reviewed Original ResearchConceptsMicroglial cellsCell toxicityPET imagingMultifactorial mechanism of actionBV2 microglial cellsDose-dependent mannerBV2 microglial cell lineMicroglial cell lineMechanism of actionF-18Multifactorial mechanismsPro-inflammatoryHigher perfusionLow perfusionRhesus macaquesCromolynCell linesIncreased uptakeTracer penetrationEnhanced uptakePotential therapeuticsPerfusionToxicityClearance assayClearanceSynthesis 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
Evaluation of the potassium channel tracer [18F]3F4AP in rhesus macaques
Guehl N, Ramos-Torres K, Linnman C, Moon S, Dhaynaut M, Wilks M, Han P, Ma C, Neelamegam R, Zhou Y, Popko B, Correia J, Reich D, Fakhri G, Herscovitch P, Normandin M, Brugarolas P. Evaluation of the potassium channel tracer [18F]3F4AP in rhesus macaques. Cerebrovascular And Brain Metabolism Reviews 2020, 41: 1721-1733. PMID: 33090071, PMCID: PMC8221756, DOI: 10.1177/0271678x20963404.Peer-Reviewed Original ResearchConceptsFocal brain injuryMyelin repair therapyContributions of demyelinationDrivers of disabilityImaging demyelinationBrain injuryMeasurements of molecular changesTool's sensitivity to changesLower myelin contentDemyelinating lesionsNeuronal conductionImpaired conductionDemyelinationBrain penetrationGold standardRhesus macaquesInjured areaMultiple sclerosisMolecular changesMyelin sheathNeurological diseasesHigh metabolic stabilityMRI methodsMRIInjury