2024
Radiosynthesis automation, non-human primate biodistribution and dosimetry of K+ channel tracer [11C]3MeO4AP
Zhou Y, Wilks M, Dhaynaut M, Guehl N, Vesper D, Moon S, Rice P, El Fakhri G, Normandin M, Brugarolas P. Radiosynthesis automation, non-human primate biodistribution and dosimetry of K+ channel tracer [11C]3MeO4AP. EJNMMI Research 2024, 14: 43. PMID: 38683467, PMCID: PMC11058135, DOI: 10.1186/s13550-024-01092-8.Peer-Reviewed Original ResearchRadiation dosimetryAverage effective doseWhole-body biodistributionTotal scan timeNon-decayEffective doseNon-human primatesSymptomatic treatment of multiple sclerosisIn vivo binding affinityBed positionTreatment of multiple sclerosisHigh-resolution CTDynamic acquisition protocolDosimetryPET dataAdult rhesus macaquesScan timeImaging demyelinationOLINDA softwareRadiationAcquisition protocolsPreclinical studiesNo significant changesHigh dosesPET imaging
2023
TauPETGen: Text-Conditional Tau PET Image Synthesis Based on Latent Diffusion Models
Jang S, Gomez C, Thibault E, Becker J, Dong Y, Normandin M, Price J, Johnson K, Fakhri G, Gong K. TauPETGen: Text-Conditional Tau PET Image Synthesis Based on Latent Diffusion Models. 2023, 00: 1-1. DOI: 10.1109/nssmicrtsd49126.2023.10338710.Peer-Reviewed Original ResearchImaging Performance of the Fully Assembled Ultra-High Resolution (UHR) Brain PET scanner
Loignon-Houle F, Toussaint M, Beaudoin J, Gaudreault M, Doyon V, Leroux J, Auger E, Thibaudeau C, Arpin L, Croteau E, Espinosa-Bentancourt E, Samson A, Bouchard J, Espagnet R, Viscogliosi N, Pepin C, Labrecque V, Paulin C, Marin T, Ouyang J, Normandin M, Tétrault M, Michaud J, Fontaine R, Fakhri G, Lecomte R. Imaging Performance of the Fully Assembled Ultra-High Resolution (UHR) Brain PET scanner. 2023, 00: 1-1. DOI: 10.1109/nssmicrtsd49126.2023.10338146.Peer-Reviewed Original ResearchBrain PET scannerUltra-high resolutionPET scannerPeak noise-equivalent count rateUltra Micro Hot Spot PhantomNoise-equivalent count rateAxial field-of-viewHot spot phantomHoffman brain phantomSmall-scale structuresCount rateBrain phantomContrast recoveryReadout schemeField of viewBrain PET imagingPhantomExcellent image qualityImaging performanceSpatial resolutionSmall structuresUltrahigh resolutionImage qualityPET imagingLarger rodsEvaluation of trans- and cis-4‑[18F]Fluorogabapentin for Brain PET Imaging
Zhou Y, Normandin M, Belov V, Macdonald-Soccorso M, Moon S, Sun Y, Fakhri G, Guehl N, Brugarolas P. Evaluation of trans- and cis-4‑[18F]Fluorogabapentin for Brain PET Imaging. ACS Chemical Neuroscience 2023, 14: 4208-4215. PMID: 37947793, DOI: 10.1021/acschemneuro.3c00593.Peer-Reviewed Original ResearchConceptsNeuropathic painRodent models of neuropathic painSubunit of voltage-dependent calcium channelsModel of neuropathic painTreatment of neuropathic painMetabolite-corrected arterial input functionVoltage-dependent calcium channelsMultilinear analysis 1Brain uptakePET imagingDose of gabapentinOne-tissue compartment modelRegional time-activity curvesAdult rhesus macaquesPlasma protein bindingTime-activity curvesModerate brain uptakeCalcium channelsInjured nerveArterial input functionGabapentinRodent modelsAnticonvulsant medicationBrain PET imagingRhesus macaquesImpact of motion correction on [18F]-MK6240 tau PET imaging
Tiss A, Marin T, Chemli Y, Spangler-Bickell M, Gong K, Lois C, Petibon Y, Landes V, Grogg K, Normandin M, Becker A, Thibault E, Johnson K, Fakhri G, Ouyang J. Impact of motion correction on [18F]-MK6240 tau PET imaging. Physics In Medicine And Biology 2023, 68: 105015. PMID: 37116511, PMCID: PMC10278956, DOI: 10.1088/1361-6560/acd161.Peer-Reviewed Original ResearchConceptsMotion correctionPET quantitationImpact of motion correctionList-mode reconstructionMotion correction methodList-mode dataMotion-corrected imagesEffect of motion correctionVoxel displacementsPhantom experimentsOptical tracking dataLong acquisitionBrain PET scansSlow motionImage qualityPET imagingPositron emission tomographyCorrectionMotionCorrection methodRates of tau accumulationHead motionMotion metricsPhantomPositronMeasurement of Cerebral Perfusion Indices from the Early Phase of [18F]MK6240 Dynamic Tau PET Imaging
Guehl N, Dhaynaut M, Hanseeuw B, Moon S, Lois C, Thibault E, Fu J, Price J, Johnson K, El Fakhri G, Normandin M. Measurement of Cerebral Perfusion Indices from the Early Phase of [18F]MK6240 Dynamic Tau PET Imaging. Journal Of Nuclear Medicine 2023, 64: 968-975. PMID: 36997330, PMCID: PMC10241011, DOI: 10.2967/jnumed.122.265072.Peer-Reviewed Original ResearchConceptsTime-activity curvesCerebral perfusionMetabolite-corrected arterial input functionBrain time-activity curvesEarly phaseRegional time-activity curvesIndices of cerebral perfusionDynamic [<sup>18</sup>FBlood-brain barrierPlasma to brain tissueStatistically significant differenceArterial blood samplesForty-nine subjectsCNArterial input functionPathophysiological mechanismsPerfusion indicatorsPET imagingBlood samplesSignificant differenceSurrogate indexNoninvasive estimationAnatomical informationCompound BForty-nine
2022
PET 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 assayClearance
2020
Positron annihilation localization by nanoscale magnetization
Gholami Y, Yuan H, Wilks M, Josephson L, El Fakhri G, Normandin M, Kuncic Z. Positron annihilation localization by nanoscale magnetization. Scientific Reports 2020, 10: 20262. PMID: 33219274, PMCID: PMC7680104, DOI: 10.1038/s41598-020-76980-9.Peer-Reviewed Original ResearchConceptsNanoscale magnetsSpatial resolution of PET imagesImproved dose localizationPositron emitting sourcesResolution of PET imagesPositron emission tomography instrumentationSpatial resolutionPositron emission tomographyAnnihilation quantaPhoton pairsPositron rangeDose localizationPositron annihilationCharged particlesOrtho-positroniumAnnihilationSuperparamagnetic iron oxide nanoparticlesCancer theranostic strategyPositron emission tomography scanPositronElectronic placesImage blurringPET imagingPET-MRITreatment outcomes
2018
[18F]Fluorocholine and [18F]Fluoroacetate PET as Imaging Biomarkers to Assess Phosphatidylcholine and Mitochondrial Metabolism in Preclinical Models of TSC and LAM
Verwer E, Kavanagh T, Mischler W, Feng Y, Takahashi K, Wang S, Shoup T, Neelamegam R, Yang J, Guehl N, Ran C, Massefski W, Cui Y, El-Chemaly S, Sadow P, Oldham W, Kijewski M, Fakhri G, Normandin M, Priolo C. [18F]Fluorocholine and [18F]Fluoroacetate PET as Imaging Biomarkers to Assess Phosphatidylcholine and Mitochondrial Metabolism in Preclinical Models of TSC and LAM. Clinical Cancer Research 2018, 24: 5925-5938. PMID: 30054282, PMCID: PMC6816044, DOI: 10.1158/1078-0432.ccr-17-3693.Peer-Reviewed Original ResearchMeSH KeywordsAgedAnimalsBiomarkersCholineDisease Models, AnimalFemaleFluoroacetatesHeterograftsHumansImage Processing, Computer-AssistedImmunohistochemistryLipid MetabolismLymphangioleiomyomatosisMaleMiceMice, TransgenicMitochondriaOxygen ConsumptionPhosphatidylcholinesPositron-Emission TomographyRatsTuberous SclerosisConceptsTuberous sclerosis complexMetabolic imaging biomarkersPreclinical modelsImaging biomarkersTSC2-deficient cellsStandardized uptake valueTuberous sclerosis complex manifestationsModels of tuberous sclerosis complexAutosomal dominant disorderPotential clinical interestBenign tumorsOvariectomized miceUptake valueSubcutaneous tumorsPreclinical studiesPulmonary nodulesCystic destructionLymphangioleiomyomatosisDominant disorderProliferative lesionsInactivating mutationsTumorMetabolic reprogrammingNeurocognitive impairmentPET imaging
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
2014
Initial in vivo PET imaging of 5-HT1A receptors with 3-[(18)F]mefway.
Wooten DW, Hillmer AT, Murali D, Barnhart TE, Thio JP, Bajwa AK, Bonab AA, Normandin MD, Schneider ML, Mukherjee J, Christian BT. Initial in vivo PET imaging of 5-HT1A receptors with 3-[(18)F]mefway. Am J Nucl Med Mol Imaging 2014, 4: 483-9. PMID: 25143866, PMCID: PMC4138142.Peer-Reviewed Original ResearchCaudal anterior cingulate gyrusMesial temporal lobePET radiotracersPET imagingAnterior cingulate gyrusDynamic PET scansVivo PET imagingMale rhesus macaquesBolus injectionCingulate gyrusPET uptakeTemporal lobePET scansLower BPNDLow affinityVivo behaviorCerebellumRhesus macaquesReceptorsSufficient uptakeReference regionSpecific bindingMinutesRadiotracerShorter scan timeMotion compensation for brain PET imaging using wireless MR active markers in simultaneous PET–MR: Phantom and non-human primate studies
Huang C, Ackerman J, Petibon Y, Normandin M, Brady T, Fakhri G, Ouyang J. Motion compensation for brain PET imaging using wireless MR active markers in simultaneous PET–MR: Phantom and non-human primate studies. NeuroImage 2014, 91: 129-137. PMID: 24418501, PMCID: PMC3965607, DOI: 10.1016/j.neuroimage.2013.12.061.Peer-Reviewed Original ResearchConceptsMotion correctionWireless markersList-mode reconstructionReconstructed PET imagesMotion correction techniqueObserver signal-to-noise ratioSimultaneous PET-MRMotion artifactsPET phantomPET contrastPET reconstructionBrain PET imagingPET imagingPhantomBrain PETPET-MRIndependent noise realizationsAccurate quantitative valuesHead motionNoise realizationsPET dataSignal-to-noise ratioStatic referenceBrain PET scansActivation markers
2010
Pancreatic Beta Cell Mass PET Imaging and Quantification with [11C]DTBZ and [18F]FP-(+)-DTBZ in Rodent Models of Diabetes
Singhal T, Ding YS, Weinzimmer D, Normandin MD, Labaree D, Ropchan J, Nabulsi N, Lin SF, Skaddan MB, Soeller WC, Huang Y, Carson RE, Treadway JL, Cline GW. Pancreatic Beta Cell Mass PET Imaging and Quantification with [11C]DTBZ and [18F]FP-(+)-DTBZ in Rodent Models of Diabetes. Molecular Imaging And Biology 2010, 13: 973-984. PMID: 20824509, PMCID: PMC3711476, DOI: 10.1007/s11307-010-0406-x.Peer-Reviewed Original Research
2005
ntPET: A New Application of PET Imaging for Characterizing the Kinetics of Endogenous Neurotransmitter Release
Morris ED, Yoder KK, Wang C, Normandin MD, Zheng QH, Mock B, Raymond F, Froehlich JC. ntPET: A New Application of PET Imaging for Characterizing the Kinetics of Endogenous Neurotransmitter Release. Molecular Imaging 2005, 4: 7290.2005.05130. PMID: 16285909, DOI: 10.2310/7290.2005.05130.Peer-Reviewed Original ResearchConceptsNeurotransmitter releaseArterial blood samplingEndogenous neurotransmitter releasePositron emission tomographyEndogenous dopamineDrug treatmentRat striatumBlood samplingBlood flowEmission tomographyFalse-positive responsesD3 receptor ligandsDopamine concentrationsPET imagingReceptor ligandsNoninvasive assayTracer kinetic modelReference regionStimulus conditionsDopamine