2024
Validation of a Simplified Tissue-to-Reference Ratio Measurement Using SUVR to Assess Synaptic Density Alterations in Alzheimer Disease with [11C]UCB-J PET
Young J, O’Dell R, Naganawa M, Toyonaga T, Chen M, Nabulsi N, Huang Y, Cooper E, Miller A, Lam J, Bates K, Ruan A, Nelsen K, Salardini E, Carson R, van Dyck C, Mecca A. Validation of a Simplified Tissue-to-Reference Ratio Measurement Using SUVR to Assess Synaptic Density Alterations in Alzheimer Disease with [11C]UCB-J PET. Journal Of Nuclear Medicine 2024, 65: jnumed.124.267419. PMID: 39299782, PMCID: PMC11533916, DOI: 10.2967/jnumed.124.267419.Peer-Reviewed Original ResearchDistribution volume ratioSUV ratioSynaptic densityEffect sizeAlzheimer's diseaseLongitudinal study of Alzheimer's diseaseMethods:</b> ParticipantsLongitudinal studyMeasure synaptic densityAD participantsStudy of Alzheimer's diseaseNormal cognitionReference regionOlder adultsMulticenterDensity alterations
2023
Assessment of Gray Matter Microstructure and Synaptic Density in Alzheimer's Disease: A Multimodal Imaging Study With DTI and SV2A PET
Silva-Rudberg J, Salardini E, O'Dell R, Chen M, Ra J, Georgelos J, Morehouse M, Melino K, Varma P, Toyonaga T, Nabulsi N, Huang Y, Carson R, van Dyck C, Mecca A. Assessment of Gray Matter Microstructure and Synaptic Density in Alzheimer's Disease: A Multimodal Imaging Study With DTI and SV2A PET. American Journal Of Geriatric Psychiatry 2023, 32: 17-28. PMID: 37673749, PMCID: PMC10840732, DOI: 10.1016/j.jagp.2023.08.002.Peer-Reviewed Original ResearchSynaptic densityAlzheimer's diseaseMean diffusivitySynaptic lossGray matter microstructureGray matter mean diffusivityDisease pathologyHippocampal synaptic densityMajor pathological correlateSetting of ADAD-related neuropathologySynaptic vesicle glycoprotein 2AHippocampal mean diffusivityAlzheimer's disease pathologyAmyloid-positive participantsMatter mean diffusivityPositron emission tomography (PET) imagingEmission Tomography ImagingGray matter structuresPathological correlatesPositive participantsInverse associationAD groupCognitive impairmentDiseasePrincipal component analysis of synaptic density measured with [11C]UCB-J PET in early Alzheimer’s disease
O'Dell R, Higgins-Chen A, Gupta D, Chen M, Naganawa M, Toyonaga T, Lu Y, Ni G, Chupak A, Zhao W, Salardini E, Nabulsi N, Huang Y, Arnsten A, Carson R, van Dyck C, Mecca A. Principal component analysis of synaptic density measured with [11C]UCB-J PET in early Alzheimer’s disease. NeuroImage Clinical 2023, 39: 103457. PMID: 37422964, PMCID: PMC10338149, DOI: 10.1016/j.nicl.2023.103457.Peer-Reviewed Original ResearchConceptsCognitive domainsCognitive performanceSubjects' scoresCortical regionsNeuropsychological batteryEarly Alzheimer's diseaseAD groupBilateral regionsNormal participantsNegative loadingsCognitive impairmentCN participantsAlzheimer's diseaseParticipantsStructural correlatesStrong contributionParticipant characteristicsScoresPositive loadingsData-driven approachTotal variancePrincipal component analysisSpecific spatial patternsInvestigating CNS distribution of PF‐05212377, a P‐glycoprotein substrate, by translation of 5‐HT6 receptor occupancy from non‐human primates to humans
Sawant‐Basak A, Chen L, Lockwood P, Boyden T, Doran A, Mancuso J, Zasadny K, McCarthy T, Morris E, Carson R, Esterlis I, Huang Y, Nabulsi N, Planeta B, Fullerton T. Investigating CNS distribution of PF‐05212377, a P‐glycoprotein substrate, by translation of 5‐HT6 receptor occupancy from non‐human primates to humans. Biopharmaceutics & Drug Disposition 2023, 44: 48-59. PMID: 36825693, DOI: 10.1002/bdd.2351.Peer-Reviewed Original ResearchConceptsNon-human primatesBrain penetrationPositron emission tomographyReceptor occupancyUnbound concentrationsPre-clinical evidenceVivo brain penetrationConcentration-dependent increaseP-glycoprotein substratesPlasma ECsP-gpAlzheimer's diseaseEmission tomographyRat BBBTarget engagementCumulative evidenceDependent increaseTransporter substratesCNS distributionBBBRatsDiseasePrimatesSpecies differencesHumans
2022
Synaptic density and cognitive performance in Alzheimer's disease: A PET imaging study with [11C]UCB‐J
Mecca AP, O'Dell RS, Sharp ES, Banks ER, Bartlett HH, Zhao W, Lipior S, Diepenbrock NG, Chen M, Naganawa M, Toyonaga T, Nabulsi NB, Vander Wyk B, Arnsten AFT, Huang Y, Carson RE, van Dyck C. Synaptic density and cognitive performance in Alzheimer's disease: A PET imaging study with [11C]UCB‐J. Alzheimer's & Dementia 2022, 18: 2527-2536. PMID: 35174954, PMCID: PMC9381645, DOI: 10.1002/alz.12582.Peer-Reviewed Original ResearchConceptsSynaptic densityEarly Alzheimer's diseaseAlzheimer's diseaseCognitive performanceMajor pathological correlateGray matter volumePositron emission tomography (PET) imagingEmission Tomography ImagingPET imaging studiesIndividual cognitive domainsNeuropathologic studiesSignificant positive associationSynapse lossSynaptic alterationsPathological correlatesNeuropsychological test performanceMatter volumeCognitive impairmentSignificant associationImaging studiesDiseaseTomography imagingGlobal cognitionStrongest predictorPositive association
2021
Association of entorhinal cortical tau deposition and hippocampal synaptic density in older individuals with normal cognition and early Alzheimer's disease
Mecca AP, Chen MK, O'Dell RS, Naganawa M, Toyonaga T, Godek TA, Harris JE, Bartlett HH, Zhao W, Banks ER, Ni GS, Rogers K, Gallezot JD, Ropchan J, Emery PR, Nabulsi NB, Vander Wyk BC, Arnsten AFT, Huang Y, Carson RE, van Dyck CH. Association of entorhinal cortical tau deposition and hippocampal synaptic density in older individuals with normal cognition and early Alzheimer's disease. Neurobiology Of Aging 2021, 111: 44-53. PMID: 34963063, PMCID: PMC8761170, DOI: 10.1016/j.neurobiolaging.2021.11.004.Peer-Reviewed Original ResearchConceptsHippocampal synaptic densitySynaptic densityAlzheimer's diseaseCortical tau depositionEarly neuropathologic changesInitial clinical featuresSynaptic vesicle glycoprotein 2AEarly Alzheimer's diseaseOverall sampleEntorhinal cortical cellsClinical featuresNeuropathologic changesTau depositionTau pathologyInverse associationPerforant pathAD groupSynaptic failureNormal cognitionOlder individualsEarly degenerationDiseaseNormal participantsHippocampusTauComparison of [11C]UCB-J and [18F]FDG PET in Alzheimer’s disease: A tracer kinetic modeling study
Chen MK, Mecca AP, Naganawa M, Gallezot JD, Toyonaga T, Mondal J, Finnema SJ, Lin SF, O’Dell R, McDonald JW, Michalak HR, Vander Wyk B, Nabulsi NB, Huang Y, Arnsten AF, van Dyck CH, Carson RE. Comparison of [11C]UCB-J and [18F]FDG PET in Alzheimer’s disease: A tracer kinetic modeling study. Cerebrovascular And Brain Metabolism Reviews 2021, 41: 2395-2409. PMID: 33757318, PMCID: PMC8393289, DOI: 10.1177/0271678x211004312.Peer-Reviewed Original ResearchConceptsSynaptic densityMedial temporal regionsAlzheimer's diseaseNeocortical regionsTemporal regionsRelative outcome measuresMedial temporal lobeVivo PET imagingJ bindingOutcome measuresTemporal lobeMagnitude of reductionCN participantsBrain regionsAD participantsDiseasePET imagingConcordant reductionNormal participantsSynaptic vesiclesPerfusionMetabolismSuitable markerParticipantsSimilar patternAssociation of Aβ deposition and regional synaptic density in early Alzheimer’s disease: a PET imaging study with [11C]UCB-J
O’Dell R, Mecca AP, Chen MK, Naganawa M, Toyonaga T, Lu Y, Godek TA, Harris JE, Bartlett HH, Banks ER, Kominek VL, Zhao W, Nabulsi NB, Ropchan J, Ye Y, Vander Wyk BC, Huang Y, Arnsten AFT, Carson RE, van Dyck CH. Association of Aβ deposition and regional synaptic density in early Alzheimer’s disease: a PET imaging study with [11C]UCB-J. Alzheimer's Research & Therapy 2021, 13: 11. PMID: 33402201, PMCID: PMC7786921, DOI: 10.1186/s13195-020-00742-y.Peer-Reviewed Original ResearchConceptsRegional Aβ depositionAβ depositionEarly Alzheimer's diseaseSynaptic lossSynaptic densityAlzheimer's diseaseDistribution volume ratioPositron emission tomographyHippocampal synaptic densityMild AD dementiaDeposition of AβSignificant inverse associationAmnestic mild cognitive impairmentWhole-brain analysisMild cognitive impairmentCerebellar reference regionPET imaging studiesPlaque burdenAD dementiaInverse associationPostmortem studiesClinical severityNeurodegenerative processesClinical diseaseLarge cohort
2020
In 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 correlatesSynthesis 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 ResearchConceptsPET 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 glycoproteinSclerosisPrognosisEpilepsyInjuryStrokeSV2APET imaging of mGluR5 in Alzheimer’s disease
Mecca AP, McDonald JW, Michalak HR, Godek TA, Harris JE, Pugh EA, Kemp EC, Chen MK, Salardini A, Nabulsi NB, Lim K, Huang Y, Carson RE, Strittmatter SM, van Dyck CH. PET imaging of mGluR5 in Alzheimer’s disease. Alzheimer's Research & Therapy 2020, 12: 15. PMID: 31954399, PMCID: PMC6969979, DOI: 10.1186/s13195-020-0582-0.Peer-Reviewed Original ResearchConceptsEarly Alzheimer's diseaseAlzheimer's diseaseMild cognitive impairmentBrain amyloidHippocampus of ADPositron emission tomography radioligandSubtype 5 receptorsMild AD dementiaGray matter atrophyAssociation cortical regionsAmnestic mild cognitive impairmentImportant therapeutic targetCerebellum reference regionDynamic PET scansHippocampal mGluR5MethodsSixteen individualsMGluR5 bindingSynaptotoxic actionAD dementiaAD pathogenesisMatter atrophyInitial administrationAD groupSynaptic transmissionEntorhinal cortex
2019
Synthesis and in vivo evaluation of [18F]UCB-J for PET imaging of synaptic vesicle glycoprotein 2A (SV2A)
Li S, Cai Z, Zhang W, Holden D, Lin SF, Finnema SJ, Shirali A, Ropchan J, Carre S, Mercier J, Carson RE, Nabulsi N, Huang Y. Synthesis and in vivo evaluation of [18F]UCB-J for PET imaging of synaptic vesicle glycoprotein 2A (SV2A). European Journal Of Nuclear Medicine And Molecular Imaging 2019, 46: 1952-1965. PMID: 31175396, PMCID: PMC6810698, DOI: 10.1007/s00259-019-04357-w.Peer-Reviewed Original ResearchConceptsSynaptic vesicle glycoprotein 2AHigh specific binding signalsNonhuman primatesPET imagingHigh brain uptakeRegional distribution volumesBrain uptakeSynaptic densityOne-tissue compartment modelExcellent imaging agentRegional time-activity curvesVivo biomarkersArterial samplesSpecific binding signalsPsychiatric diseasesTime-activity curvesAlzheimer's diseaseDistribution volumeNeuropsychiatric disordersRadioactive metabolitesRhesus monkeysPET radiotracersVivo evaluationDiseaseImaging agentEvaluation of 11C-LSN3172176 as a Novel PET Tracer for Imaging M1 Muscarinic Acetylcholine Receptors in Nonhuman Primates
Nabulsi NB, Holden D, Zheng MQ, Bois F, Lin SF, Najafzadeh S, Gao H, Ropchan J, Lara-Jaime T, Labaree D, Shirali A, Slieker L, Jesudason C, Barth V, Navarro A, Kant N, Carson RE, Huang Y. Evaluation of 11C-LSN3172176 as a Novel PET Tracer for Imaging M1 Muscarinic Acetylcholine Receptors in Nonhuman Primates. Journal Of Nuclear Medicine 2019, 60: 1147-1153. PMID: 30733324, DOI: 10.2967/jnumed.118.222034.Peer-Reviewed Original ResearchConceptsMuscarinic acetylcholine receptorsAcetylcholine receptorsNonhuman primatesM1 muscarinic acetylcholine receptorBrain time-activity curvesRich brain regionsArterial blood samplingNovel PET tracersSuitable reference regionRegional distribution volumesReference regionDevelopment of drugsBrain uptakeGlobus pallidusDistribution volume valuesNucleus accumbensBlood samplingPET scansTime-activity curvesCognitive impairmentAlzheimer's diseaseBrain regionsDistribution volumeSelective radiotracerRhesus monkeys
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 propertiesLevetiracetamAssessing 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 measures
2017
Cortical β-amyloid burden, gray matter, and memory in adults at varying APOE ε4 risk for Alzheimer's disease
Mecca AP, Barcelos NM, Wang S, Brück A, Nabulsi N, Planeta-Wilson B, Nadelmann J, Benincasa AL, Ropchan J, Huang Y, Gelernter J, Van Ness PH, Carson RE, van Dyck CH. Cortical β-amyloid burden, gray matter, and memory in adults at varying APOE ε4 risk for Alzheimer's disease. Neurobiology Of Aging 2017, 61: 207-214. PMID: 29111487, PMCID: PMC5722236, DOI: 10.1016/j.neurobiolaging.2017.09.027.Peer-Reviewed Original ResearchConceptsΒ-amyloid burdenMiddle-aged individualsAβ burdenEpisodic memory performanceCognitive declineGM fractionCortical β-amyloid burdenBrain magnetic resonance imagingFirst-degree family historyCortical Aβ burdenGray matter fractionNormal middle-aged individualsSubsequent cognitive declineMagnetic resonance imagingPositron emission tomographyAPOE ε3ε3Cortical AβCerebral amyloidosisAPOE genotypeFamily historyPreclinical ADMemory performanceNeuropsychological testingAlzheimer's diseaseGray matter
2016
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 ResearchConceptsSynaptic 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 studies