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
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 ligandsSynthesis 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
Quantification of Myocardial Mitochondrial Membrane Potential Using PET
Pelletier-Galarneau M, Detmer F, Petibon Y, Normandin M, Ma C, Alpert N, El Fakhri G. Quantification of Myocardial Mitochondrial Membrane Potential Using PET. Current Cardiology Reports 2021, 23: 70. PMID: 33970353, PMCID: PMC8443083, DOI: 10.1007/s11886-021-01500-8.Peer-Reviewed Original ResearchThe cortical origin and initial spread of medial temporal tauopathy in Alzheimer’s disease assessed with positron emission tomography
Sanchez J, Becker J, Jacobs H, Hanseeuw B, Jiang S, Schultz A, Properzi M, Katz S, Beiser A, Satizabal C, O'Donnell A, DeCarli C, Killiany R, El Fakhri G, Normandin M, Gómez-Isla T, Quiroz Y, Rentz D, Sperling R, Seshadri S, Augustinack J, Price J, Johnson K. The cortical origin and initial spread of medial temporal tauopathy in Alzheimer’s disease assessed with positron emission tomography. Science Translational Medicine 2021, 13 PMID: 33472953, PMCID: PMC7978042, DOI: 10.1126/scitranslmed.abc0655.Peer-Reviewed Original ResearchConceptsPositron emission tomographyTemporal lobeMedial temporal lobe tauAlzheimer's diseaseMedial temporal lobeStudy of normal agingAssociated with baseline measuresMolecular positron emission tomographyTau-PET signalDegree of clinical impairmentEmission tomographyModel of Alzheimer's diseaseTemporal lobe anatomyCognitive declineClinical impairmentNormal agingAdult participantsStudy of AgingRhinal sulcusBrain pathologyExtratemporal regionsPET measurementsLongitudinal studyTau progressionClinically normal people
2020
Joint Direct Parametric Reconstruction for Pet Receptor Occupancy Mapping
Marin T, Ouyang J, Fakhri G, Normandin M, Petibon Y. Joint Direct Parametric Reconstruction for Pet Receptor Occupancy Mapping. 2020, 00: 1-4. DOI: 10.1109/nss/mic42677.2020.9507742.Peer-Reviewed Original ResearchCentral nervous systemPositron emission tomographyVariable splitting techniqueReceptor occupancyBayesian reconstruction frameworkDenoising problemDose-occupancy relationshipReconstruction frameworkCentral nervous system drugsDevelopment of central nervous systemEstimation of receptor occupancyOptimization problemDrug brain penetrationLow precisionMeasure occupancyDrug AdministrationBrain penetrationRadiation exposureSplitting techniqueEmission tomographyDynamic dataTracer bindingNervous systemConventional approachesTarget engagementIn-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
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
Synthesis and preliminary PET imaging of 11C and 18F isotopologues of the ROS1/ALK inhibitor lorlatinib
Collier T, Normandin M, Stephenson N, Livni E, Liang S, Wooten D, Esfahani S, Stabin M, Mahmood U, Chen J, Wang W, Maresca K, Waterhouse R, El Fakhri G, Richardson P, Vasdev N. Synthesis and preliminary PET imaging of 11C and 18F isotopologues of the ROS1/ALK inhibitor lorlatinib. Nature Communications 2017, 8: 15761. PMID: 28594000, PMCID: PMC5472746, DOI: 10.1038/ncomms15761.Peer-Reviewed Original ResearchMeSH KeywordsAminopyridinesAnaplastic Lymphoma KinaseAnimalsCarbon RadioisotopesChemistry Techniques, SyntheticContrast MediaFluorine RadioisotopesHumansIsotope LabelingLactamsLactams, MacrocyclicMacaca mulattaMaleMicePositron-Emission TomographyProtein-Tyrosine KinasesProto-Oncogene ProteinsPyrazolesTissue DistributionXenograft Model Antitumor AssaysConceptsAnaplastic lymphoma kinasePositron emission tomographyPositron emission tomography imagingC-ros oncogene 1Non-small cell lung cancerCell lung cancerBrain tumor lesionsOptimal therapeutic outcomesLung cancer patientsBlood-brain barrierPF-06463922Clinical trial investigatorsTumor uptakeLung cancerSmall molecule inhibitorsCancer patientsTherapeutic outcomesLorlatinibEmission tomographyDosimetry assessmentNon-human primatesTrial investigatorsBrain permeabilityEarly goalRadiolabeling strategiesBrain Penetration of the ROS1/ALK Inhibitor Lorlatinib Confirmed by PET
Collier T, Maresca K, Normandin M, Richardson P, McCarthy T, Liang S, Waterhouse R, Vasdev N. Brain Penetration of the ROS1/ALK Inhibitor Lorlatinib Confirmed by PET. Molecular Imaging 2017, 16: 1536012117736669. PMID: 29067878, PMCID: PMC5661750, DOI: 10.1177/1536012117736669.Peer-Reviewed Original ResearchConceptsPositron emission tomographyLung cancerTreatment of non-small-cell lung cancerBrain metastases of patientsNon-small-cell lung cancerPositron emission tomography evaluationNonhuman primatesRodent tumor modelsGoal of clinical translationOptimal therapeutic outcomesMetastasis of patientsBlood-brain barrierBrain metastasesPF-06463922Preclinical modelsClinical trial investigatorsTumor modelMolecular alterationsLorlatinibTherapeutic outcomesCancer therapeuticsBrain penetrationClinical translationEmission tomographyTrial investigators
2016
A Bayesian spatial temporal mixtures approach to kinetic parametric images in dynamic positron emission tomography
Zhu W, Ouyang J, Rakvongthai Y, Guehl N, Wooten D, Fakhri G, Normandin M, Fan Y. A Bayesian spatial temporal mixtures approach to kinetic parametric images in dynamic positron emission tomography. Medical Physics 2016, 43: 1222-1234. PMID: 26936707, PMCID: PMC5025019, DOI: 10.1118/1.4941010.Peer-Reviewed Original ResearchConceptsPositron emission tomographySpatial mixture modelNearby voxelsMixture modelEmission tomographyDynamic positron emission tomographyK-means methodKinetic modelKinetic parametric imagesOne-compartment kinetic modelNovel algorithmTemporal informationClassification purposesMeasurement of local perfusionLocal perfusionTime activity curvesNormal ROIsTemporal modelBayesian algorithmCardiac studiesMarkov chain Monte CarloParameter estimationNoise regionSimulation experimentsSimulated data sets
2015
Heat‐Induced Radiolabeling of Nanoparticles for Monocyte Tracking by PET
Normandin M, Yuan H, Wilks M, Chen H, Kinsella J, Cho H, Guehl N, Absi‐Halabi N, Hosseini S, Fakhri G, Sosnovik D, Josephson L. Heat‐Induced Radiolabeling of Nanoparticles for Monocyte Tracking by PET. Angewandte Chemie 2015, 127: 13194-13198. DOI: 10.1002/ange.201505525.Peer-Reviewed Original ResearchPositron emission tomographyRadiolabelling of nanoparticlesStandardized uptake valueMonocytes in vitroNP pharmacokineticsSlow uptake processUptake valueLymph nodesCirculating monocytesMonocyte traffickingIV injectionImmune responseBlood clearanceEmission tomographyHepatic uptakeMonocytesPharmacokineticsLymphUptake processHeat‐Induced Radiolabeling of Nanoparticles for Monocyte Tracking by PET
Normandin M, Yuan H, Wilks M, Chen H, Kinsella J, Cho H, Guehl N, Absi‐Halabi N, Hosseini S, Fakhri G, Sosnovik D, Josephson L. Heat‐Induced Radiolabeling of Nanoparticles for Monocyte Tracking by PET. Angewandte Chemie International Edition 2015, 54: 13002-13006. PMID: 26368132, PMCID: PMC4754124, DOI: 10.1002/anie.201505525.Peer-Reviewed Original ResearchConceptsPositron emission tomographyRadiolabelling of nanoparticlesStandardized uptake valueNP pharmacokineticsSlow uptake processUptake valueLymph nodesCirculating monocytesMonocyte traffickingIV injectionImmune responseBlood clearanceEmission tomographyHepatic uptakeMonocytesPharmacokineticsLymphUptake processCytometry
2014
Synthesis of the dopamine D2/D3 receptor agonist (+)-PHNO via supercritical fluid chromatography: preliminary PET imaging study with [3-11C]-(+)PHNO
Shoup T, McCauley J, Lee D, Chen R, Normandin M, Bonab A, Fakhri G, Vasdev N. Synthesis of the dopamine D2/D3 receptor agonist (+)-PHNO via supercritical fluid chromatography: preliminary PET imaging study with [3-11C]-(+)PHNO. Tetrahedron Letters 2014, 55: 682-685. DOI: 10.1016/j.tetlet.2013.11.113.Peer-Reviewed Original ResearchPositron emission tomography imaging studiesSupercritical fluid chromatographyPositron emission tomographyFluid chromatographyImaging studiesAgonist radiopharmaceuticalsDopamine receptorsEnantiomeric resolutionDopamineCarbon-11Emission tomographyAdipose tissueBrown adipose tissueIn vivoBrown fatSynthesis
2013
Neurovascular coupling to D2/D3 dopamine receptor occupancy using simultaneous PET/functional MRI
Sander C, Hooker J, Catana C, Normandin M, Alpert N, Knudsen G, Vanduffel W, Rosen B, Mandeville J. Neurovascular coupling to D2/D3 dopamine receptor occupancy using simultaneous PET/functional MRI. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 11169-11174. PMID: 23723346, PMCID: PMC3703969, DOI: 10.1073/pnas.1220512110.Peer-Reviewed Original ResearchConceptsFunctional magnetic resonance imagingDopamine receptor occupancyReceptor occupancyPositron emission tomographyFunctional magnetic resonance imaging measuresDose of racloprideBasal dopamine levelsDopamine-rich striatumInvestigation of neurovascular couplingDomains of spaceAnesthetized nonhuman primatesSimultaneous PET/fMRIDopamine levelsBrain activitySimultaneous neuroimagingBinding potentialBasal gangliaReceptor systemNonhuman primatesPositron emission tomography tracersMagnetic resonance imagingLiterature differencesEmission tomographyMap associationsNeurovascular couplingElevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: a positron emission tomography study
Neumeister A, Normandin MD, Pietrzak RH, Piomelli D, Zheng MQ, Gujarro-Anton A, Potenza MN, Bailey CR, Lin SF, Najafzadeh S, Ropchan J, Henry S, Corsi-Travali S, Carson RE, Huang Y. Elevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: a positron emission tomography study. Molecular Psychiatry 2013, 18: 1034-1040. PMID: 23670490, PMCID: PMC3752332, DOI: 10.1038/mp.2013.61.Peer-Reviewed Original ResearchMeSH KeywordsAdultAmidesAnalysis of VarianceArachidonic AcidsBrainEndocannabinoidsEthanolaminesFemaleGlyceridesHumansHydrocortisoneImidazolesLogistic ModelsMalePalmitic AcidsPiperidinesPolyunsaturated AlkamidesPyrazolesRadionuclide ImagingReceptor, Cannabinoid, CB1Stress Disorders, Post-TraumaticYoung AdultConceptsPost-traumatic stress disorderVolume of distributionCB1 receptor availabilityPositron emission tomographyHC groupReceptor availabilityTC groupCannabinoid type 1 receptorStress disorderPositron emission tomography studyEvidence-based pharmacotherapyEtiology of PTSDType 1 receptorEmission tomography studiesAnandamide concentrationsElevated brainPeripheral levelsHealthy controlsCB1 receptorsUntreated individualsPET scansAnimal modelsCortisol levelsLifetime historyEmission tomography
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
2007
Heterogeneous Effects of Alcohol on Dopamine Release in the Striatum: A PET Study
Yoder KK, Constantinescu CC, Kareken DA, Normandin MD, Cheng T, O'Connor SJ, Morris ED. Heterogeneous Effects of Alcohol on Dopamine Release in the Striatum: A PET Study. Alcohol Clinical And Experimental Research 2007, 31: 965-973. PMID: 17428296, DOI: 10.1111/j.1530-0277.2007.00390.x.Peer-Reviewed Original ResearchConceptsAnatomic extentDA responseDA releasePositron emission tomographyAlcohol-related behaviorsDopaminergic responseDopamine releaseD2/D3 receptor availabilityStriatal dopamine releaseHealthy control subjectsStriatal DA responseStriatal binding potentialD3 receptor availabilityTime-Line FollowSubjective responsesVoxel-wise t-testsEffects of alcoholControl subjectsAlcohol infusionPET scansReceptor availabilityEmission tomographyLack of reportsDA involvementPET studies