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
2023
Tau Positron Emission Tomography and Neurocognitive Function Among Former Professional American-Style Football Players
Dhaynaut M, Grashow R, Normandin M, Wu O, Marengi D, Terry D, Sanchez J, Weisskopf M, Speizer F, Taylor H, Guehl N, Seshadri S, Beiser A, Daneshvar D, Johnson K, Iverson G, Zafonte R, Fakhri G, Baggish A. Tau Positron Emission Tomography and Neurocognitive Function Among Former Professional American-Style Football Players. Journal Of Neurotrauma 2023, 40: 1614-1624. PMID: 37282582, PMCID: PMC10458363, DOI: 10.1089/neu.2022.0454.Peer-Reviewed Original ResearchConceptsPositron emission tomographyDistribution volume ratioNeuropsychological testsNeurocognitive functionStandardized uptake value ratioControl participantsMeasures of neurocognitive functionStructural magnetic resonance imagingMeasures of memoryDepressive symptom severityMale control participantsEmission tomographyCerebellar gray matterNeuropsychological measuresTau positron emission tomographyExecutive functionSymptom severityBrain regionsEntorhinal cortexRepetitive head impactsP-tauReference regionFormer playersRepetitive head impact exposureMale controls
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 kinetics
2019
Novel radioligands for imaging sigma-1 receptor in brain using positron emission tomography (PET)
Lan Y, Bai P, Chen Z, Neelamegam R, Placzek M, Wang H, Fiedler S, Yang J, Yuan G, Qu X, Schmidt H, Song J, Normandin M, Ran C, Wang C. Novel radioligands for imaging sigma-1 receptor in brain using positron emission tomography (PET). Acta Pharmaceutica Sinica B 2019, 9: 1204-1215. PMID: 31867166, PMCID: PMC6900558, DOI: 10.1016/j.apsb.2019.07.002.Peer-Reviewed Original ResearchPositron emission tomographySigma-1 receptorCentral nervous systemPET/CT imagingEmission tomographyOrgans of micePositron emission tomography tracersNeuropsychiatric disordersNon-invasive quantificationBrain regionsNoninvasive toolSigma-1RadioligandDisease pathophysiologyNervous systemNovel radioligandMiceMouse brainPathological conditionsBrainReceptorsTomographyIntracellular proteinsTarget validationPET/CT
2017
Lessons learned about [F-18]-AV-1451 off-target binding from an autopsy-confirmed Parkinson’s case
Marquié M, Verwer E, Meltzer A, Kim S, Agüero C, Gonzalez J, Makaretz S, Siao Tick Chong M, Ramanan P, Amaral A, Normandin M, Vanderburg C, Gomperts S, Johnson K, Frosch M, Gómez-Isla T. Lessons learned about [F-18]-AV-1451 off-target binding from an autopsy-confirmed Parkinson’s case. Acta Neuropathologica Communications 2017, 5: 75. PMID: 29047416, PMCID: PMC5648451, DOI: 10.1186/s40478-017-0482-0.Peer-Reviewed Original ResearchConceptsPositron emission tomographyBasal gangliaBinding to neuromelaninPositron emission tomography studiesDementia of AD typeInferior temporal cortexParkinson's diseaseTau pathologyPositron emission tomography scanAlzheimer's diseaseMild cognitive impairmentTemporal cortexAutoradiographic bindingBrain regionsNeurofibrillary tau pathologyOccipital cortexPositron emission tomography signalCognitive impairmentPostmortem materialEntorhinal cortexSubstantia nigraParenchymal hemorrhagePD diagnosisAutoradiography experimentsChoroid plexus[F-18]-AV-1451 binding correlates with postmortem neurofibrillary tangle Braak staging
Marquié M, Siao Tick Chong M, Antón-Fernández A, Verwer E, Sáez-Calveras N, Meltzer A, Ramanan P, Amaral A, Gonzalez J, Normandin M, Frosch M, Gómez-Isla T. [F-18]-AV-1451 binding correlates with postmortem neurofibrillary tangle Braak staging. Acta Neuropathologica 2017, 134: 619-628. PMID: 28612291, PMCID: PMC5772971, DOI: 10.1007/s00401-017-1740-8.Peer-Reviewed Original ResearchConceptsNeurofibrillary tanglesNeurofibrillary tau pathologyTau burdenBraak stageStaging of neurofibrillary tanglesBrain regionsAccurate diagnosis of Alzheimer's diseaseTau pathologyPhospho-tauStereotyped spatiotemporal patternBraak NFT stageNeurofibrillary tangle Braak stagePhosphor-screen autoradiographyAlzheimer's diseaseMild cognitive impairmentTau measuresNFT stageCognitively normal controlsObserved patternBraakCognitive impairmentWestern blottingBindingDiagnosis of Alzheimer's diseaseBraak staging of neurofibrillary tanglesPathological correlations of [F‐18]‐AV‐1451 imaging in non‐alzheimer tauopathies
Marquié M, Normandin M, Meltzer A, Chong M, Andrea N, Antón‐Fernández A, Klunk W, Mathis C, Ikonomovic M, Debnath M, Bien E, Vanderburg C, Costantino I, Makaretz S, DeVos S, Oakley D, Gomperts S, Growdon J, Domoto‐Reilly K, Lucente D, Dickerson B, Frosch M, Hyman B, Johnson K, Gómez‐Isla T. Pathological correlations of [F‐18]‐AV‐1451 imaging in non‐alzheimer tauopathies. Annals Of Neurology 2017, 81: 117-128. PMID: 27997036, PMCID: PMC5319193, DOI: 10.1002/ana.24844.Peer-Reviewed Original ResearchConceptsNon-Alzheimer tauopathiesTau lesionsDetection of tau aggregatesBinding to tau lesionsTau measuresPositron emission tomographyMutation carriersTau filamentsProgressive supranuclear palsyTau aggregationPostmortem brain samplesAlzheimer brainsTauopathiesAV-1451Atypical tauopathyBrain regionsOff-target bindingBinding patternsBinding assaysBasal gangliaEntorhinal cortexSubstantia nigraTauMAPT
2012
Positron Emission Tomography Shows Elevated Cannabinoid CB 1 Receptor Binding in Men with Alcohol Dependence
Neumeister A, Normandin MD, Murrough JW, Henry S, Bailey CR, Luckenbaugh DA, Tuit K, Zheng M, Galatzer‐Levy I, Sinha R, Carson RE, Potenza MN, Huang Y. Positron Emission Tomography Shows Elevated Cannabinoid CB 1 Receptor Binding in Men with Alcohol Dependence. Alcohol Clinical And Experimental Research 2012, 36: 2104-2109. PMID: 22551199, PMCID: PMC3418442, DOI: 10.1111/j.1530-0277.2012.01815.x.Peer-Reviewed Original ResearchConceptsPositron emission tomographyAlcohol dependenceBrain CBTime-activity curvesEmission tomographyBody mass indexHealthy control menRecent therapeutic developmentsMedication-free participantsPosterior cingulate cortexCurrent study designPreclinical evidenceSmoking statusMass indexControl menReceptor densityLast drinkECB functionCingulate cortexBrain regionsSelective radiotracerEndogenous CBOrbitofrontal cortexPeripheral measuresStudy design