Featured Publications
Imaging synaptic density in the living human brain
Finnema SJ, Nabulsi NB, Eid T, Detyniecki K, Lin SF, Chen MK, Dhaher R, Matuskey D, Baum E, Holden D, Spencer DD, Mercier J, Hannestad J, Huang Y, Carson RE. Imaging synaptic density in the living human brain. Science Translational Medicine 2016, 8: 348ra96. PMID: 27440727, DOI: 10.1126/scitranslmed.aaf6667.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBrainEpilepsyFemaleHumansMaleMembrane GlycoproteinsMiddle AgedNerve Tissue ProteinsPositron-Emission TomographySynapsesConceptsSynaptic densityPositron emission tomographyPET imagingSynaptic vesicle glycoprotein 2ATemporal lobe epilepsyNumerous brain disordersCentral nervous systemNumber of synapsesJ PET imagingHuman brainHuman PET studiesPredominant neuronsSurgical resectionSynaptic lossLobe epilepsyPsychiatric disordersNervous systemBrain disordersPresynaptic boutonsAlzheimer's diseaseBrain tissueEmission tomographyNeuron contactsTherapeutic monitoringPET studiesAssessing Synaptic Density in Alzheimer Disease With Synaptic Vesicle Glycoprotein 2A Positron Emission Tomographic Imaging
Chen MK, Mecca AP, Naganawa M, Finnema SJ, Toyonaga T, Lin SF, Najafzadeh S, Ropchan J, Lu Y, McDonald JW, Michalak HR, Nabulsi NB, Arnsten AFT, Huang Y, Carson RE, van Dyck CH. Assessing Synaptic Density in Alzheimer Disease With Synaptic Vesicle Glycoprotein 2A Positron Emission Tomographic Imaging. JAMA Neurology 2018, 75: 1215-1224. PMID: 30014145, PMCID: PMC6233853, DOI: 10.1001/jamaneurol.2018.1836.Peer-Reviewed Original ResearchConceptsPositron emission tomographic imagingSynaptic vesicle glycoprotein 2ASynaptic densityAlzheimer's diseaseEmission tomographic imagingHigh-resolution PET scanningPET scanningCognitive impairmentDisease-modifying therapiesDisease-modifying treatmentsNormal participantsCross-sectional studyPittsburgh compound BMajor structural correlateAmnestic mild cognitive impairmentMagnetic resonance imagingMild cognitive impairmentJ PET imagingRestoration of synapsesSpecific bindingNeurologic evaluationSynaptic lossDisease stagePostmortem studiesOutcome measuresReduced synaptic vesicle protein 2A binding in temporal lobe epilepsy: A [11C]UCB‐J positron emission tomography study
Finnema SJ, Toyonaga T, Detyniecki K, Chen M, Dias M, Wang Q, Lin S, Naganawa M, Gallezot J, Lu Y, Nabulsi NB, Huang Y, Spencer DD, Carson RE. Reduced synaptic vesicle protein 2A binding in temporal lobe epilepsy: A [11C]UCB‐J positron emission tomography study. Epilepsia 2020, 61: 2183-2193. PMID: 32944949, DOI: 10.1111/epi.16653.Peer-Reviewed Original ResearchConceptsMedial temporal lobe sclerosisTemporal lobe epilepsyTLE subjectsPositron emission tomographyLobe epilepsyJ BPSynaptic vesicle protein 2APartial volume correctionTemporal lobe sclerosisPositron emission tomography studyEmission tomography studiesSeizure onset zonePromising biomarker approachJ bindingPresurgical selectionSclerotic hippocampusHippocampal asymmetryTLE patientsRegional binding patternsControl subjectsCentrum semiovaleContralateral regionsEpilepsy patientsOutcome measuresOnset zoneLower synaptic density is associated with depression severity and network alterations
Holmes SE, Scheinost D, Finnema SJ, Naganawa M, Davis MT, DellaGioia N, Nabulsi N, Matuskey D, Angarita GA, Pietrzak RH, Duman RS, Sanacora G, Krystal JH, Carson RE, Esterlis I. Lower synaptic density is associated with depression severity and network alterations. Nature Communications 2019, 10: 1529. PMID: 30948709, PMCID: PMC6449365, DOI: 10.1038/s41467-019-09562-7.Peer-Reviewed Original ResearchConceptsMajor depressive disorderPost-traumatic stress disorderLower synaptic densitySynaptic densityPositron emission tomographyFunctional connectivityNetwork alterationsSynaptic vesicle glycoprotein 2ASymptoms of depressionSynaptic lossDepressive disorderHealthy controlsNerve terminalsDepressive symptomsDepression severityUnmedicated individualsSynaptic connectionsEmission tomographyStress disorderVivo evidenceSymptomsDepressionSeverityDisordersAlterations
2023
Reductions in synaptic marker SV2A in early-course Schizophrenia
Yoon J, Zhang Z, Mormino E, Davidzon G, Minzenberg M, Ballon J, Kalinowski A, Hardy K, Naganawa M, Carson R, Khalighi M, Park J, Levinson D, Chin F. Reductions in synaptic marker SV2A in early-course Schizophrenia. Journal Of Psychiatric Research 2023, 161: 213-217. PMID: 36934603, DOI: 10.1016/j.jpsychires.2023.02.026.Peer-Reviewed Original ResearchMeSH KeywordsBrainFrontal LobeHippocampusHumansMembrane GlycoproteinsNerve Tissue ProteinsPositron-Emission TomographySchizophreniaTemporal LobeConceptsChronic patientsSynaptic pruningStage of illnessEarly course patientsEarly course schizophreniaSeverity of delusionsWidespread reductionMajor disease mechanismsSynaptic deficitsSynaptic markersSynaptic eliminationPET scansFormal onsetBrain regionsSignificant positive correlationPatientsSchizophrenia studiesSchizophreniaDisease mechanismsCognitive performanceIllnessEarly phaseSpecific bindingPresent studyPositive correlation
2022
Imaging of Synaptic Density in Neurodegenerative Disorders
Carson RE, Naganawa M, Toyonaga T, Koohsari S, Yang Y, Chen MK, Matuskey D, Finnema SJ. Imaging of Synaptic Density in Neurodegenerative Disorders. Journal Of Nuclear Medicine 2022, 63: 60s-67s. PMID: 35649655, DOI: 10.2967/jnumed.121.263201.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAnimalsHumansMembrane GlycoproteinsMiceNerve Tissue ProteinsPositron-Emission TomographyRadiopharmaceuticalsRatsConceptsSynaptic densityAlzheimer's diseaseNeurodegenerative disordersNeurodegenerative diseasesSynaptic vesicle protein 2APotential reference regionsSynaptic density lossLewy body dementiaProgressive supranuclear palsyDisease-modifying therapiesSpecific brain proteinsLarge patient cohortAntiepileptic drug levetiracetamPET imaging resultsMultiple neurodegenerative disordersSynaptic lossSupranuclear palsyCorticobasal degenerationNeuropathologic diseasePatient cohortRat modelClinical valueF-FDGParkinson's diseaseEfficacy assessmentImaging the fetal nonhuman primate brain with SV2A positron emission tomography (PET)
Rossano S, Toyonaga T, Berg E, Lorence I, Fowles K, Nabulsi N, Ropchan J, Li S, Ye Y, Felchner Z, Kukis D, Huang Y, Benveniste H, Tarantal AF, Groman S, Carson RE. Imaging the fetal nonhuman primate brain with SV2A positron emission tomography (PET). European Journal Of Nuclear Medicine And Molecular Imaging 2022, 49: 3679-3691. PMID: 35633376, PMCID: PMC9826644, DOI: 10.1007/s00259-022-05825-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainMacaca mulattaMembrane GlycoproteinsNerve Tissue ProteinsPositron-Emission TomographyConceptsPositron emission tomographySynaptic densityFetal brainThird trimesterEmission tomographyBrain developmentGravid rhesus monkeysPost-mortem brain tissueEarly neonatal periodNonhuman primate brainLate gestational periodSubset of subjectsPostnatal brain developmentPost-mortem samplesGestational ageNeonatal periodPregnant monkeysSynapse numberGestational periodPrimary motorPrimate brainBrain growthSubcortical regionsBrain tissueCortical regions
2021
Identifying brain networks in synaptic density PET (11C-UCB-J) with independent component analysis
Fang XT, Toyonaga T, Hillmer AT, Matuskey D, Holmes SE, Radhakrishnan R, Mecca AP, van Dyck CH, D’Souza D, Esterlis I, Worhunsky PD, Carson RE. Identifying brain networks in synaptic density PET (11C-UCB-J) with independent component analysis. NeuroImage 2021, 237: 118167. PMID: 34000404, PMCID: PMC8452380, DOI: 10.1016/j.neuroimage.2021.118167.Peer-Reviewed Original ResearchConceptsSynaptic densityResting-state functional magnetic resonance imagingSynaptic vesicle protein 2ALevel-dependent signal fluctuationsBrain networksFunctional magnetic resonance imagingMagnetic resonance imagingAge-related changesHealthy controlsResonance imagingRs-fMRIEffects of sexProtein 2AMultiple comparisonsHuman brainAgePotential utilitySexFirst evidenceCovariance patterns
2020
Quantification of SV2A Binding in Rodent Brain Using [18F]SynVesT-1 and PET Imaging
Sadasivam P, Fang XT, Toyonaga T, Lee S, Xu Y, Zheng MQ, Spurrier J, Huang Y, Strittmatter SM, Carson RE, Cai Z. Quantification of SV2A Binding in Rodent Brain Using [18F]SynVesT-1 and PET Imaging. Molecular Imaging And Biology 2020, 23: 372-381. PMID: 33258040, PMCID: PMC8105262, DOI: 10.1007/s11307-020-01567-9.Peer-Reviewed Original ResearchConceptsBrain stemAlzheimer's diseaseMin postinjectionAnimal modelsAPP/PS1 miceReference regionStandardized uptake value ratioDynamic PET imaging dataUptake value ratioRodent brain tissueStatic PET scansDifferent imaging windowsPET imaging dataWild-type controlsReference tissue modelPS1 miceAD pathogenesisTherapeutic effectMouse modelRodent modelsLittermate controlsPET scansRodent brainPreclinical imaging studiesTherapeutic drug efficacyBinding of the synaptic vesicle radiotracer [11C]UCB-J is unchanged during functional brain activation using a visual stimulation task
Smart K, Liu H, Matuskey D, Chen MK, Torres K, Nabulsi N, Labaree D, Ropchan J, Hillmer AT, Huang Y, Carson RE. Binding of the synaptic vesicle radiotracer [11C]UCB-J is unchanged during functional brain activation using a visual stimulation task. Cerebrovascular And Brain Metabolism Reviews 2020, 41: 1067-1079. PMID: 32757741, PMCID: PMC8054713, DOI: 10.1177/0271678x20946198.Peer-Reviewed Original ResearchConceptsVisual cortexVisual stimulationPositron emission tomography radioligandBrain activationBlood flow increasesVolume of distributionPrimary visual cortexCheckerboard visual stimulationFunctional brain activationFunctional magnetic resonanceReference tissue modelFMRI BOLD responsesSynaptic densityVisual stimulation taskOne-tissue compartment modelHealthy volunteersNeuronal firingTomography radioligandPET scansTissue influxVivo measuresRobust increaseBOLD responseTracer influxStimulation taskIn vivo measurement of widespread synaptic loss in Alzheimer's disease with SV2A PET
Mecca AP, Chen M, O'Dell RS, Naganawa M, Toyonaga T, Godek TA, Harris JE, Bartlett HH, Zhao W, Nabulsi NB, Vander Wyk B, Varma P, Arnsten AFT, Huang Y, Carson RE, van Dyck C. In vivo measurement of widespread synaptic loss in Alzheimer's disease with SV2A PET. Alzheimer's & Dementia 2020, 16: 974-982. PMID: 32400950, PMCID: PMC7383876, DOI: 10.1002/alz.12097.Peer-Reviewed Original ResearchConceptsWidespread synaptic lossEarly Alzheimer's diseaseSynaptic lossAlzheimer's diseaseSynaptic vesicle glycoprotein 2AGray matter volumeMajor structural correlatePositron emission tomography (PET) imagingEmission Tomography ImagingDistribution volume ratioCerebellar reference regionNeocortical brain regionsSynaptic densityAD progressionConsistent pathologyPotential therapyMatter volumePromising biomarkerCognitive impairmentCN participantsBrain regionsDiseaseTomography imagingNormal participantsStructural correlatesSynaptic Changes in Parkinson Disease Assessed with in vivo Imaging
Matuskey D, Tinaz S, Wilcox KC, Naganawa M, Toyonaga T, Dias M, Henry S, Pittman B, Ropchan J, Nabulsi N, Suridjan I, Comley RA, Huang Y, Finnema SJ, Carson RE. Synaptic Changes in Parkinson Disease Assessed with in vivo Imaging. Annals Of Neurology 2020, 87: 329-338. PMID: 31953875, PMCID: PMC7065227, DOI: 10.1002/ana.25682.Peer-Reviewed Original ResearchConceptsSubstantia nigraParkinson's diseaseNormal controlsSynaptic changesPositron emission tomographic imagingSynaptic vesicle glycoprotein 2AParkinson's disease groupParkinson's disease subjectsEmission tomographic imagingPrimary brain areasAnn NeurolPostmortem autoradiographyBilateral diseaseNonmotor symptomsSynaptic lossNeuronal alterationsRelevant cortical areasStriatal dopamineBrainstem nucleiDisease groupDopamine neuronsLocus coeruleusCortical areasRed nucleusDopamine systemSynthesis and Preclinical Evaluation of an 18F‑Labeled Synaptic Vesicle Glycoprotein 2A PET Imaging Probe: [18F]SynVesT‑2
Cai Z, Li S, Zhang W, Pracitto R, Wu X, Baum E, Finnema SJ, Holden D, Toyonaga T, Lin SF, Lindemann M, Shirali A, Labaree DC, Ropchan J, Nabulsi N, Carson RE, Huang Y. Synthesis and Preclinical Evaluation of an 18F‑Labeled Synaptic Vesicle Glycoprotein 2A PET Imaging Probe: [18F]SynVesT‑2. ACS Chemical Neuroscience 2020, 11: 592-603. PMID: 31961649, DOI: 10.1021/acschemneuro.9b00618.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAnimalsBrainEpilepsyHumansMembrane GlycoproteinsNerve Tissue ProteinsPrimatesSynaptic VesiclesConceptsPET imaging probeHigh specific binding signalsNon-human primate brainSynaptic vesicle glycoprotein 2ATraumatic brain injuryPost-traumatic stress disorderMultiple sclerosisBrain injuryParkinson's diseasePreclinical evaluationSpecific binding signalsPrimate brainAlzheimer's diseaseNeuropsychiatric diseasesPresynaptic vesiclesStress disorderDiseaseImaging probeTransmembrane glycoproteinSclerosisPrognosisEpilepsyInjuryStrokeSV2A
2019
Assessment of a white matter reference region for 11C-UCB-J PET quantification
Rossano S, Toyonaga T, Finnema SJ, Naganawa M, Lu Y, Nabulsi N, Ropchan J, De Bruyn S, Otoul C, Stockis A, Nicolas JM, Martin P, Mercier J, Huang Y, Maguire RP, Carson RE. Assessment of a white matter reference region for 11C-UCB-J PET quantification. Cerebrovascular And Brain Metabolism Reviews 2019, 40: 1890-1901. PMID: 31570041, PMCID: PMC7446568, DOI: 10.1177/0271678x19879230.Peer-Reviewed Original ResearchA single‐center, open‐label positron emission tomography study to evaluate brivaracetam and levetiracetam synaptic vesicle glycoprotein 2A binding in healthy volunteers
Finnema SJ, Rossano S, Naganawa M, Henry S, Gao H, Pracitto R, Maguire RP, Mercier J, Kervyn S, Nicolas J, Klitgaard H, DeBruyn S, Otoul C, Martin P, Muglia P, Matuskey D, Nabulsi NB, Huang Y, Kaminski RM, Hannestad J, Stockis A, Carson RE. A single‐center, open‐label positron emission tomography study to evaluate brivaracetam and levetiracetam synaptic vesicle glycoprotein 2A binding in healthy volunteers. Epilepsia 2019, 60: 958-967. PMID: 30924924, PMCID: PMC6532410, DOI: 10.1111/epi.14701.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAnticonvulsantsCarbon RadioisotopesFemaleHealthy VolunteersHumansInhibitory Concentration 50Injections, IntravenousLevetiracetamMagnetic Resonance ImagingMaleMembrane GlycoproteinsNerve Tissue ProteinsNeuroimagingPositron-Emission TomographyProtein BindingPyrrolidinonesConceptsSynaptic vesicle glycoprotein 2AIntravenous brivaracetamHours postdoseBrain penetrationHealthy volunteersDaily oral dosingPositron emission tomography studyFurther clinical studiesEmission tomography studiesPlasma concentration relationshipPositron emission tomography (PET) tracerEmission tomography tracerVivo animal studiesAcute seizuresAntiepileptic drugsTherapeutic dosesCohort 2Oral dosingCohort 1Clinical studiesCohort 3LevetiracetamAnimal studiesRelevant dosesBrivaracetam
2018
Synthesis and in Vivo Evaluation of a Novel PET Radiotracer for Imaging of Synaptic Vesicle Glycoprotein 2A (SV2A) in Nonhuman Primates
Li S, Cai Z, Wu X, Holden D, Pracitto R, Kapinos M, Gao H, Labaree D, Nabulsi N, Carson RE, Huang Y. Synthesis and in Vivo Evaluation of a Novel PET Radiotracer for Imaging of Synaptic Vesicle Glycoprotein 2A (SV2A) in Nonhuman Primates. ACS Chemical Neuroscience 2018, 10: 1544-1554. PMID: 30396272, PMCID: PMC6810685, DOI: 10.1021/acschemneuro.8b00526.Peer-Reviewed Original ResearchConceptsSynaptic vesicle glycoprotein 2AStandardized uptake valuePET radiotracersNonhuman primatesAlterations of synapsesC-UCBPeak standardized uptake valueVivo evaluationHigh brain uptakeNovel PET radiotracersBrain uptakeSynaptic densityExcellent radiotracerPsychiatric disordersUptake valueCingulate cortexAlzheimer's diseaseBrain disordersNovel radiotracersRhesus monkeysNeurodegenerative diseasesTissue kineticsDiseaseAttractive imaging propertiesLevetiracetam
2017
Kinetic evaluation and test–retest reproducibility of [11C]UCB-J, a novel radioligand for positron emission tomography imaging of synaptic vesicle glycoprotein 2A in humans
Finnema SJ, Nabulsi NB, Mercier J, Lin SF, Chen MK, Matuskey D, Gallezot JD, Henry S, Hannestad J, Huang Y, Carson RE. Kinetic evaluation and test–retest reproducibility of [11C]UCB-J, a novel radioligand for positron emission tomography imaging of synaptic vesicle glycoprotein 2A in humans. Cerebrovascular And Brain Metabolism Reviews 2017, 38: 2041-2052. PMID: 28792356, PMCID: PMC6259313, DOI: 10.1177/0271678x17724947.Peer-Reviewed Original Research
2016
Synthesis and Preclinical Evaluation of 11C-UCB-J as a PET Tracer for Imaging the Synaptic Vesicle Glycoprotein 2A in the Brain
Nabulsi N, Mercier J, Holden D, Carré S, Najafzadeh S, Vandergeten MC, Lin SF, Deo A, Price N, Wood M, Lara-Jaime T, Montel F, Laruelle M, Carson RE, Hannestad J, Huang Y. Synthesis and Preclinical Evaluation of 11C-UCB-J as a PET Tracer for Imaging the Synaptic Vesicle Glycoprotein 2A in the Brain. Journal Of Nuclear Medicine 2016, 57: 777-784. PMID: 26848175, DOI: 10.2967/jnumed.115.168179.Peer-Reviewed Original ResearchConceptsSynaptic vesicle glycoprotein 2AWhole-body biodistributionPET radiotracersNonhuman primatesDose-limiting organHigher free fractionGray matter regionsBaseline VTNondisplaceable distribution volumeAntiepileptic drugsVitro inhibition constantSynaptic densityPreclinical evaluationMonkey brainDistribution volumeArterial samplingEndocrine cellsRegional volumesMatter regionsRhesus macaquesPET tracersUCBFree fractionBrainTarget occupancy
2015
Brivaracetam, a selective high‐affinity synaptic vesicle protein 2A (SV2A) ligand with preclinical evidence of high brain permeability and fast onset of action
Nicolas JM, Hannestad J, Holden D, Kervyn S, Nabulsi N, Tytgat D, Huang Y, Chanteux H, Staelens L, Matagne A, Mathy FX, Mercier J, Stockis A, Carson RE, Klitgaard H. Brivaracetam, a selective high‐affinity synaptic vesicle protein 2A (SV2A) ligand with preclinical evidence of high brain permeability and fast onset of action. Epilepsia 2015, 57: 201-209. PMID: 26663401, DOI: 10.1111/epi.13267.Peer-Reviewed Original ResearchConceptsFaster onsetAcute seizuresHigh-affinity synaptic vesicle protein 2A ligandNonhuman primate PET studyAudiogenic seizure miceRapid brain entryOnset of actionSingle oral dosingHigh brain permeabilityBlood-brain barrier permeability (BBBP) valuesPrimate PET studyAudiogenic miceBrain entryCaco-2 cellsSeizure micePreclinical evidenceAntiepileptic drugsSusceptible miceBrain levelsBrain penetrationPreclinical dataBrain kineticsOral dosingSingle dosingClinical studies
2003
Linearized Reference Tissue Parametric Imaging Methods: Application to [11C]DASB Positron Emission Tomography Studies of the Serotonin Transporter in Human Brain
Ichise M, Liow JS, Lu JQ, Takano A, Model K, Toyama H, Suhara T, Suzuki K, Innis RB, Carson RE. Linearized Reference Tissue Parametric Imaging Methods: Application to [11C]DASB Positron Emission Tomography Studies of the Serotonin Transporter in Human Brain. Cerebrovascular And Brain Metabolism Reviews 2003, 23: 1096-1112. PMID: 12973026, DOI: 10.1097/01.wcb.0000085441.37552.ca.Peer-Reviewed Original Research