2024
Advances and Insights in Positron Emission Tomography Tracers for Metabotropic Glutamate Receptor 4 Imaging
Wang J, Li Y, Fakhri G. Advances and Insights in Positron Emission Tomography Tracers for Metabotropic Glutamate Receptor 4 Imaging. Journal Of Medicinal Chemistry 2024, 67: 10517-10529. PMID: 38924702, PMCID: PMC11290609, DOI: 10.1021/acs.jmedchem.3c02431.Peer-Reviewed Original ResearchConceptsPositive allosteric modulatorsPositron emission tomographyPositron emission tomography radioligandsAllosteric modulatorsMGluR4 positive allosteric modulatorsMetabotropic glutamate receptor subtype 4PET ligandNeurological disordersPositron emission tomography tracersEmission tomographySubtype 4Molecular imaging modalitiesEffective treatmentMetabotropicDisordersParent drugImaging modalitiesPET tracersMGluR4Therapeutic targetPositron emitting radioisotopesSelection of lead compoundsLiving subjectsPositronQuantitative accuracyPET 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 controlsFully automated radiosynthesis of [18F]mG4P027 for mGluR4 imaging
Moon S, Fakhri G, Zhang Z, Brownell A, Wang J. Fully automated radiosynthesis of [18F]mG4P027 for mGluR4 imaging. IRADIOLOGY 2023, 1: 120-127. PMID: 37496513, PMCID: PMC10371389, DOI: 10.1002/ird3.25.Peer-Reviewed Original Research
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 ResearchQuantitative PET in the 2020s: a roadmap
Meikle S, Sossi V, Roncali E, Cherry S, Banati R, Mankoff D, Jones T, James M, Sutcliffe J, Ouyang J, Petibon Y, Ma C, El Fakhri G, Surti S, Karp J, Badawi R, Yamaya T, Akamatsu G, Schramm G, Rezaei A, Nuyts J, Fulton R, Kyme A, Lois C, Sari H, Price J, Boellaard R, Jeraj R, Bailey D, Eslick E, Willowson K, Dutta J. Quantitative PET in the 2020s: a roadmap. Physics In Medicine And Biology 2021, 66: 06rm01. PMID: 33339012, PMCID: PMC9358699, DOI: 10.1088/1361-6560/abd4f7.Peer-Reviewed Original ResearchMeSH KeywordsArtificial IntelligenceHistory, 20th CenturyHistory, 21st CenturyHumansImage Processing, Computer-AssistedImaging, Three-DimensionalKineticsMedical OncologyNeoplasmsPositron Emission Tomography Computed TomographyPositron-Emission TomographyPrognosisRadiopharmaceuticalsSystems BiologyTomography, X-Ray ComputedConceptsTime-of-flight positron emission tomographyStatistical image reconstructionTotal-body positron emission tomographyPositron emission tomographyQuantitative positron emission tomographyImage reconstructionWhole-body positron emission tomographySensitivity of positron emission tomographyCapabilities of positron emission tomographyImage qualityClinical applicationTracer principleRelevant parametersOncology applicationsPhysicsStatistical qualityExpansion of applicationsEmission tomographyClinical practicePET/MRBiologically relevant parametersSensitive biomarkerPositronThe 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 equilibriumSynthesis and Characterization of Fluorine-18-Labeled N‑(4-Chloro-3-((fluoromethyl‑d 2)thio)phenyl)picolinamide for Imaging of mGluR4 in Brain
Wang J, Qu X, Shoup T, Yuan G, Afshar S, Pan C, Zhu A, Choi J, Kang H, Poutiainen P, Fakhri G, Zhang Z, Brownell A. Synthesis and Characterization of Fluorine-18-Labeled N‑(4-Chloro-3-((fluoromethyl‑d 2)thio)phenyl)picolinamide for Imaging of mGluR4 in Brain. Journal Of Medicinal Chemistry 2020, 63: 3381-3389. PMID: 32081008, PMCID: PMC7261135, DOI: 10.1021/acs.jmedchem.0c00201.Peer-Reviewed Original ResearchConceptsDrug-like propertiesMethylthio analoguePotential ligandsMetabolic stabilityPositron emission tomographyRadiochemical yieldMolar activityDose-dependent blocking effectPositron emission tomography imaging studiesMethylthioPAM activityBrain regionsMale Sprague Dawley ratsLigandEx vivo biodistribution studiesRadiosynthesisSprague Dawley ratsBrainMGluR4SynthesisAnaloguesEmission tomographyImaging studies
2019
New Detector Designs for High Resolution Brain PET
Bläckberg L, Sajedi S, Fakhri G, Sabet H. New Detector Designs for High Resolution Brain PET. 2019, 00: 1-5. DOI: 10.1109/nss/mic42101.2019.9059785.Peer-Reviewed Original ResearchLaser induced optical barriersLYSO:Ce crystalsScintillation light spreadIntrinsic resolutionDetector designCe crystalsOptical barrierBrain positron emission tomographyScintillationCrystal thicknessPhotodetector elementsTransverse resolutionDetectorPositron emission tomographyPhotodetectorsImproved positionLYSOCrystalReadoutResolutionLaserDependenceEmission tomographyQuantification of PET Myocardial Blood Flow
Pelletier-Galarneau M, Martineau P, El Fakhri G. Quantification of PET Myocardial Blood Flow. Current Cardiology Reports 2019, 21: 11. PMID: 30815744, DOI: 10.1007/s11886-019-1096-x.Peer-Reviewed Original ResearchConceptsPositron emission tomographyMyocardial blood flowMyocardial flow reserveMicrovascular dysfunctionEvaluation of cardiac allograft vasculopathyAssessment of coronary microvascular dysfunctionFlow reserveHyperemic myocardial blood flowFlow quantificationCardiac allograft vasculopathyMarkers of disease severityCoronary microvascular dysfunctionImprove risk stratificationQuantification of myocardial blood flowFractional flow reserveMyocardial blood flow quantificationAllograft vasculopathyPrognostic valueRisk stratificationEpicardial diseaseAcademic centersReviewThe aimClinical aspectsEmission tomographyBlood flow
2017
Guest Editorial Low-Dose CT: What Has Been Done, and What Challenges Remain?
Liang J, La Riviere P, Fakhri G, Glick S, Siewerdsen J. Guest Editorial Low-Dose CT: What Has Been Done, and What Challenges Remain? IEEE Transactions On Medical Imaging 2017, 36: 2409-2416. DOI: 10.1109/tmi.2017.2768978.Peer-Reviewed Original ResearchCone-beam CTMulti-detector row CTDiscovery of X-raysIntroduction of computed tomographyMonitoring of therapeutic responseMulti-detector-rowImage-guided interventionsProjection dataMagnetic resonance imagingPositron emission tomographyTherapeutic responseEmergency examinationTreatment planningVolumetric imagesDiagnostic imagingEmission tomographyImaging modalitiesResonance imagingX-rayMedical imaging modalitiesCTTomographyTomographic imagesPositronSynthesis 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 strategiesMonte Carlo simulation of PET/MR scanner and assessment of motion correction strategies
şın A, Ozsahin D, Dutta J, Haddani S, El-Fakhri G. Monte Carlo simulation of PET/MR scanner and assessment of motion correction strategies. Journal Of Instrumentation 2017, 12: c03089-c03089. DOI: 10.1088/1748-0221/12/03/c03089.Peer-Reviewed Original ResearchMotion correction strategiesGATE simulationsMonte Carlo simulationsImage qualityPET/MR scannersPositron emission tomographyPET acquisitionImage reconstruction methodMotion compensation methodEmission tomographyImaging modalitiesAcquisition timeExtraction algorithmReference imageRespiratory movementsTumor detectionGateReconstruction methodPatient movement
2016
Tissue-Specific Near-Infrared Fluorescence Imaging
Owens E, Henary M, Fakhri G, Choi H. Tissue-Specific Near-Infrared Fluorescence Imaging. Accounts Of Chemical Research 2016, 49: 1731-1740. PMID: 27564418, PMCID: PMC5776714, DOI: 10.1021/acs.accounts.6b00239.Peer-Reviewed Original ResearchConceptsSingle-photon emission computed tomographyPositron emission tomographyVital tissuesReal-time intraoperative navigationReal-time image guidanceContrast agentsTargeted NIR fluorophoresEmission computed tomographyTissue-specific contrast agentsEffective imaging agentsTissue-specific targetingReal-time delineationIntraoperative successTargeted therapyImage guidanceTumor tissuesEPR effectIntraoperative navigationSurgical fieldClinical imaging technologyDiagnostic utilityClinical useEmission tomographySurgical spaceTarget tissuesA 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