2024
Presynaptic terminal integrity is associated with glucose metabolism in Parkinson’s disease
Wang W, Wang Y, Xu L, Liu X, Hu Y, Li J, Huang Q, Ren S, Huang Y, Guan Y, Li Y, Hua F, Ye Q, Xie F. Presynaptic terminal integrity is associated with glucose metabolism in Parkinson’s disease. European Journal Of Nuclear Medicine And Molecular Imaging 2024, 1-10. PMID: 39572432, DOI: 10.1007/s00259-024-06993-3.Peer-Reviewed Original ResearchPositron emission tomographyDopamine transporterSynaptic densityGlucose metabolismDopamine transporter availabilityPD patientsPost-commissural caudateParkinson's diseaseReduced synaptic densityAssociated with glucose metabolismDopaminergic transporterMethodsA totalHealthy controlsSynaptic vesicle protein 2PatientsEmission tomographyCaudatePD groupMetabolic patternsTerminal integrityProtein 2DiseaseNC groupCaudate regionsMetabolism11C-UCB-J PET imaging is consistent with lower synaptic density in autistic adults
Matuskey D, Yang Y, Naganawa M, Koohsari S, Toyonaga T, Gravel P, Pittman B, Torres K, Pisani L, Finn C, Cramer-Benjamin S, Herman N, Rosenthal L, Franke C, Walicki B, Esterlis I, Skosnik P, Radhakrishnan R, Wolf J, Nabulsi N, Ropchan J, Huang Y, Carson R, Naples A, McPartland J. 11C-UCB-J PET imaging is consistent with lower synaptic density in autistic adults. Molecular Psychiatry 2024, 1-7. PMID: 39367053, DOI: 10.1038/s41380-024-02776-2.Peer-Reviewed Original ResearchPositron emission tomographySynaptic densityAutistic adultsBrain regionsAutistic featuresClinical phenotype of autismNon-autistic participantsPhenotype of autismNon-autistic individualsRelationship to clinical characteristicsSynaptic vesicle glycoprotein 2AAssociated with clinical measuresPost-mortem studiesPositron emission tomography scanPrefrontal cortexClinician ratingsAutism groupNeural basisBrain areasNeural processesBetween-group differencesVolumetric differencesBinding potentialDensity of synapsesAutismNoninvasive quantification of [18F]SynVesT-1 binding using simplified reference tissue model 2
Naganawa M, Gallezot J, Li S, Nabulsi N, Henry S, Cai Z, Matuskey D, Huang Y, Carson R. Noninvasive quantification of [18F]SynVesT-1 binding using simplified reference tissue model 2. European Journal Of Nuclear Medicine And Molecular Imaging 2024, 1-9. PMID: 39155309, DOI: 10.1007/s00259-024-06885-6.Peer-Reviewed Original ResearchPositron emission tomographyCentrum semiovaleReference regionPositron emission tomography scanTest-retest variabilityTest-retest reproducibilitySynaptic vesicle glycoprotein 2AOne-tissue compartmentArterial blood samplesRetest scansGold standardBrain uptakeEmission tomographyBlood samplesCerebellumNoninvasive quantificationSRTM2ConclusionOur findingsPopulation averageHealthy participantsMetabolite analysisScan timeBPNDSemiovaleLoss of synaptic density in nucleus basalis of meynert indicates distinct neurodegeneration in Alzheimer’s disease: the RJNB-D study
Li B, Chen H, Zheng Y, Xu X, You Z, Huang Q, Huang Y, Guan Y, Zhao J, Liu J, Xie F, Wang J, Xu W, Zhang J, Deng Y. Loss of synaptic density in nucleus basalis of meynert indicates distinct neurodegeneration in Alzheimer’s disease: the RJNB-D study. European Journal Of Nuclear Medicine And Molecular Imaging 2024, 1-11. PMID: 39112615, DOI: 10.1007/s00259-024-06862-z.Peer-Reviewed Original ResearchWhite matter tractsCognitive impairmentSynaptic densityCognitive performancePositron emission tomographyNucleus basalisSeverity of cognitive impairmentAlzheimer's diseaseSynaptic lossNucleus basalis of MeynertBasalis of MeynertSynaptic vesicle glycoprotein 2Pathogenesis of Alzheimer's diseaseStandardized uptake value ratioCholinergic systemProfile of ADCN participantsPotential impairmentMMSE scoreMedial tractNBMImpairmentEmission tomographyLoss of synaptic densityNormal controlsTau pathology is associated with synaptic density and longitudinal synaptic loss in Alzheimer’s disease
Wang J, Huang Q, Chen X, You Z, He K, Guo Q, Huang Y, Yang Y, Lin Z, Guo T, Zhao J, Guan Y, Li B, Xie F. Tau pathology is associated with synaptic density and longitudinal synaptic loss in Alzheimer’s disease. Molecular Psychiatry 2024, 29: 2799-2809. PMID: 38589563, DOI: 10.1038/s41380-024-02501-z.Peer-Reviewed Original ResearchTau pathologySynaptic lossTau tanglesAlzheimer's diseaseAssociated with synaptic lossAD patientsMild cognitive impairmentMild cognitive impairment patientsAmyloid-bPlasma p-tauP-tau181 levelsAssociation of ABSynaptic densityP-tauNormal controlsPositron emission tomographyMediation analysisTemporal lobeTauTau burdenP-tau181One-year follow-up assessmentSeventy-five participantsTanglesFollow-up assessmentAPOE ε4 is associated with decreased synaptic density in cognitively impaired participants
He K, Li B, Wang J, Wang Y, You Z, Chen X, Chen H, Li J, Huang Q, Guo Q, Huang Y, Guan Y, Chen K, Zhao J, Deng Y, Xie F. APOE ε4 is associated with decreased synaptic density in cognitively impaired participants. Alzheimer's & Dementia 2024, 20: 3157-3166. PMID: 38477490, PMCID: PMC11095422, DOI: 10.1002/alz.13775.Peer-Reviewed Original ResearchApolipoprotein E4Tau pathologyAlzheimer's diseaseApo E4AD biomarkersAPOE e4 allele carriersAmyloid-betaEffects of apolipoprotein E4Synaptic lossAPOE e4 alleleSynaptic densitySynaptic density lossNon-carriersE4 alleleE4 allele carriersE4 genotypeTauGenotypesPositron emission tomographyAllele carriersMedial temporal lobeAllelesAmyloidEffect of APOE E4Cognitively impaired participantsA pilot study to evaluate the effect of CT1812 treatment on synaptic density and other biomarkers in Alzheimer’s disease
van Dyck C, Mecca A, O’Dell R, Bartlett H, Diepenbrock N, Huang Y, Hamby M, Grundman M, Catalano S, Caggiano A, Carson R. A pilot study to evaluate the effect of CT1812 treatment on synaptic density and other biomarkers in Alzheimer’s disease. Alzheimer's Research & Therapy 2024, 16: 20. PMID: 38273408, PMCID: PMC10809445, DOI: 10.1186/s13195-024-01382-2.Peer-Reviewed Original ResearchConceptsMild to moderate dementiaPositron emission tomographyAlzheimer's diseaseVolumetric MRIModerate dementiaClinical rating scalesSynaptic vesicle glycoprotein 2ACerebrospinal fluidMouse model of ADPharmacodynamic effectsPlacebo-controlled phase 1 clinical trialBiomarkers of AD pathologyClinical trialsCognitive measuresNominally significant differencesPhase 1 clinical trialModel of ADHippocampal cortexPhase 1/2 studyRating ScaleParallel-group trialSynaptic densityTrial registrationThe clinical trialPlacebo-controlledSigma-2 receptor ligandsImaging a putative marker of brain cortisol regulation in alcohol use disorder
Verplaetse T, Hillmer A, Bhatt S, Rusowicz A, Li S, Nabulsi N, Matuskey D, Huang Y, McKee S, Cosgrove K. Imaging a putative marker of brain cortisol regulation in alcohol use disorder. Neurobiology Of Stress 2024, 29: 100609. PMID: 38304303, PMCID: PMC10832501, DOI: 10.1016/j.ynstr.2024.100609.Peer-Reviewed Original ResearchAlcohol use disorderAnterior cingulate cortexDrinking days/weekModerate to severe alcohol use disorderHealthy controlsHypothalamic-pituitary-adrenal (HPA) axisSevere alcohol use disorderPositron emission tomographyHPA axis dysfunctionHPA axis functionRelease of glucocorticoid hormonesAlcohol consumptionAssociated with drinkingVentromedial PFCCingulate cortexHigh-resolution research tomographHPA activityUse disorderDrinking episodesCortisol regulationAxis functionVmPFCPeripheral cortisolBrain availabilityDisordered background
2023
Imaging the brain’s immune response to alcohol with [11C]PBR28 TSPO Positron Emission Tomography
Raval N, Angarita G, Matuskey D, Miller R, Drake L, Kapinos M, Nabulsi N, Huang Y, Carson R, O’Malley S, Cosgrove K, Hillmer A. Imaging the brain’s immune response to alcohol with [11C]PBR28 TSPO Positron Emission Tomography. Molecular Psychiatry 2023, 28: 3384-3390. PMID: 37532797, PMCID: PMC10743097, DOI: 10.1038/s41380-023-02198-6.Peer-Reviewed Original ResearchConceptsVolume of distributionBlood alcohol levelsPositron emission tomographyBrain immune responseImmune responseAlcohol challengeEmission tomographyPeak blood alcohol levelsMultilinear analysis 1Peripheral immune functionVivo human evidenceLaboratory alcohol challengeTSPO positron emission tomographyBinge levelsPlasma cytokinesImmune dysfunctionNeuroimmune systemIL-6MCP-1Cytokines TNFAcute effectsScan dayArterial bloodHuman evidenceImmune functionPreclinical evaluation of a brain penetrant PARP PET imaging probe in rat glioblastoma and nonhuman primates
Chen B, Ojha D, Toyonaga T, Tong J, Pracitto R, Thomas M, Liu M, Kapinos M, Zhang L, Zheng M, Holden D, Fowles K, Ropchan J, Nabulsi N, De Feyter H, Carson R, Huang Y, Cai Z. Preclinical evaluation of a brain penetrant PARP PET imaging probe in rat glioblastoma and nonhuman primates. European Journal Of Nuclear Medicine And Molecular Imaging 2023, 50: 2081-2099. PMID: 36849748, DOI: 10.1007/s00259-023-06162-y.Peer-Reviewed Original ResearchConceptsPositron emission tomographyHealthy nonhuman primatesVolume of distributionDistribution volume ratioBrain kineticsRat glioblastoma modelPreclinical evaluationBrain regionsGlioblastoma modelPET tracersNonhuman primatesTumor-bearing ratsEx vivo biodistributionPET imaging resultsActive clinical trialsTreatment of glioblastomaHigh specific uptakeDynamic PET scansNoninvasive quantificationBrain positron emission tomographyNondisplaceable volumeBrain penetrationLow nonspecific uptakePrognostic informationClinical trialsInvestigating 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 differencesHumansIn Vivo Imaging and Kinetic Modeling of Novel Glycogen Synthase Kinase-3 Radiotracers [11C]OCM-44 and [18F]OCM-50 in Non-Human Primates
Smart K, Zheng M, Holden D, Felchner Z, Zhang L, Han Y, Ropchan J, Carson R, Vasdev N, Huang Y. In Vivo Imaging and Kinetic Modeling of Novel Glycogen Synthase Kinase-3 Radiotracers [11C]OCM-44 and [18F]OCM-50 in Non-Human Primates. Pharmaceuticals 2023, 16: 194. PMID: 37259346, PMCID: PMC9959234, DOI: 10.3390/ph16020194.Peer-Reviewed Original ResearchPositron emission tomographyNon-human primatesMetabolite-corrected arterial input functionML/Free fractionWarrants further evaluationPotential therapeutic targetGood brain uptakeAdult rhesus macaquesPlasma free fractionArterial blood samplingGray matter regionsTwo-tissue compartment modelBrain uptakeRegional time-activity curvesBlood samplingPsychiatric disordersPET scansTherapeutic targetTime-activity curvesGray matterBrain regionsEmission tomographyFurther evaluationArterial input functionSerotonin transporter availability in physically aggressive personality disordered patients: associations with trait and state aggression, and response to fluoxetine
Rosell D, Slifstein M, Thompson J, Xu X, Perez-Rodriguez M, McClure M, Hazlett E, New A, Nabulsi N, Huang Y, Carson R, Siever L, Abi-Dargham A, Koenigsberg H. Serotonin transporter availability in physically aggressive personality disordered patients: associations with trait and state aggression, and response to fluoxetine. Psychopharmacology 2023, 240: 361-371. PMID: 36640190, DOI: 10.1007/s00213-022-06306-2.Peer-Reviewed Original ResearchConceptsAnterior cingulate cortexAnti-aggressive effectsIED patientsPositron emission tomographyVentral striatumTransporter availabilityChildhood traumaSerotonin transporter availabilityRational treatment selectionIntermittent explosive disorderFluoxetine 20Fluoxetine treatmentSerotonergic abnormalitiesHealthy comparison participantsTreatment selectionRisk individualsObjectivesThe aimPatientsCingulate cortexExplosive disorderEmission tomographyImpulsive aggressionNovel therapeuticsFluoxetineNeuroanatomical basis
2021
Low-Dose Augmentation With Buprenorphine for Treatment-Resistant Depression: A Multisite Randomized Controlled Trial With Multimodal Assessment of Target Engagement
Lee H, Blumberger D, Lenze E, Anderson S, Barch D, Black K, Cristancho P, Daskalakis Z, Eisenstein S, Huang Y, Li S, Lissemore J, McConathy J, Mulsant B, Rajji T, Reynolds C, Su Y, Tu Z, Voineskos D, Karp J. Low-Dose Augmentation With Buprenorphine for Treatment-Resistant Depression: A Multisite Randomized Controlled Trial With Multimodal Assessment of Target Engagement. Biological Psychiatry Global Open Science 2021, 2: 127-135. PMID: 36325158, PMCID: PMC9616305, DOI: 10.1016/j.bpsgos.2021.09.003.Peer-Reviewed Original ResearchTranscranial magnetic stimulation measuresTreatment-resistant depressionPositron emission tomographyFunctional magnetic resonanceTarget engagementClinical trialsCortical transmissionMontgomery-Åsberg Depression Rating ScalePlacebo-controlled clinical trialEmission tomographyLow-dose augmentationVenlafaxine extended releasePrimary outcome measureBlood oxygen level-dependent (BOLD) responseMajor depressive episodeDepression Rating ScaleExperimental therapeutic approachesYears of ageMultimodal assessmentLevel-dependent responsesMonetary incentive delay taskBrain positron emission tomographyPlacebo groupIncentive delay taskClinical effectsChapter 15 Positron emission tomography imaging agents for evaluating the pathologic features of Alzheimer's disease and drug development
Huang Y, Jia H, Bao W. Chapter 15 Positron emission tomography imaging agents for evaluating the pathologic features of Alzheimer's disease and drug development. 2021, 367-412. DOI: 10.1016/b978-0-12-816475-4.00013-6.Peer-Reviewed Original ResearchAlzheimer's diseasePathologic featuresApplication of PETDrug developmentSynaptic vesicle protein 2ADifferent pathologic featuresFeatures of neurodegenerationCentral nervous systemAD drug developmentPositron emission tomographyNeuroinflammation biomarkersCholinergic systemΒ-amyloidNervous systemTau proteinEmission tomographyAD researchDiseaseProtein 2AInvestigation of diseasesQuantitative imaging techniquesTomographyImaging techniquesAgentsPET
2020
PET Imaging of Synaptic Vesicle Protein 2A
Finnema S, Li S, Cai Z, Naganawa M, Chen M, Matuskey D, Nabulsi N, Esterlis I, Holmes S, Radhakrishnan R, Toyonaga T, Huang Y, Carson R. PET Imaging of Synaptic Vesicle Protein 2A. 2020, 993-1019. DOI: 10.1007/978-3-030-53176-8_29.ChaptersSynaptic vesicle protein 2APositron emission tomographyAntiepileptic drug levetiracetamInitial PET studiesPET imagingPET studiesSynaptic densityDrug levetiracetamHigh-affinity SV2A ligandsBrain regionsSynaptic density lossNeuropathological diseasesDisease-modifying therapiesLarge patient cohortMajor depressive disorderProtein 2APET imaging resultsPosttraumatic stress disorderPatient groupPatient cohortDepressive disorderClinical valueParkinson's diseaseEfficacy assessmentSynaptic vesicle proteins
2019
The Kappa Opioid Receptor Is Associated With Naltrexone-Induced Reduction of Drinking and Craving
de Laat B, Goldberg A, Shi J, Tetrault JM, Nabulsi N, Zheng MQ, Najafzadeh S, Gao H, Kapinos M, Ropchan J, O'Malley SS, Huang Y, Morris ED, Krishnan-Sarin S. The Kappa Opioid Receptor Is Associated With Naltrexone-Induced Reduction of Drinking and Craving. Biological Psychiatry 2019, 86: 864-871. PMID: 31399255, DOI: 10.1016/j.biopsych.2019.05.021.Peer-Reviewed Original ResearchConceptsKappa-opioid receptorsAlcohol use disorderOpioid receptorsUse disordersNonselective opioid receptor antagonistModest clinical effectsEfficacy of naltrexoneOpioid receptor antagonistDSM-IV criteriaPositron emission tomographyAlcohol Urge QuestionnaireNaltrexone initiationNaltrexone therapyClinical effectsReceptor antagonistTherapeutic effectCingulate cortexDrinking paradigmHeavy drinkersBilateral insulaNaltrexoneAlcohol dependenceBrain regionsEmission tomographyPrefrontal cortex
2017
Systemic inflammation enhances stimulant-induced striatal dopamine elevation
Petrulli J, Kalish B, Nabulsi N, Huang Y, Hannestad J, Morris E. Systemic inflammation enhances stimulant-induced striatal dopamine elevation. Translational Psychiatry 2017, 7: e1076-e1076. PMID: 28350401, PMCID: PMC5404612, DOI: 10.1038/tp.2017.18.Peer-Reviewed Original ResearchMeSH KeywordsAdultCarbon RadioisotopesCase-Control StudiesCentral Nervous System StimulantsDopamineDopamine AntagonistsFemaleHealthy VolunteersHumansInflammationInterleukin-6Interleukin-8LipopolysaccharidesMaleMethylphenidateNeostriatumPositron-Emission TomographyRacloprideRadiopharmaceuticalsReceptors, Dopamine D2Tumor Necrosis Factor-alphaYoung AdultConceptsDA elevationSystemic inflammationImmune activationTumor necrosis factor alphaAcute immune activationImmune activator lipopolysaccharideOral methylphenidate (MPH) challengeStriatal DA levelsIL-8 concentrationsNecrosis factor alphaMesolimbic dopamine systemCross-over designPositron emission tomographyNeuroimmune systemMethylphenidate challengeDA levelsDA transmissionDopamine elevationDA dysfunctionFactor alphaBaseline scanHealthy subjectsAntagonist tracersPlaceboDopamine system
2003
Imaging Human Mesolimbic Dopamine Transmission with Positron Emission Tomography. Part II: Amphetamine-Induced Dopamine Release in the Functional Subdivisions of the Striatum
Martinez D, Slifstein M, Broft A, Mawlawi O, Hwang DR, Huang Y, Cooper T, Kegeles L, Zarahn E, Abi-Dargham A, Haber SN, Laruelle M. Imaging Human Mesolimbic Dopamine Transmission with Positron Emission Tomography. Part II: Amphetamine-Induced Dopamine Release in the Functional Subdivisions of the Striatum. Cerebrovascular And Brain Metabolism Reviews 2003, 23: 285-300. PMID: 12621304, DOI: 10.1097/01.wcb.0000048520.34839.1a.Peer-Reviewed Original ResearchConceptsD2 receptor availabilityPositron emission tomographyReceptor availabilityHuman striatumFunctional subdivisionsDopamine releaseAssociative regionsSensorimotor regionsEmission tomographyAmphetamine-induced dopamine releaseIntegration of limbicMesolimbic dopamine transmissionDopamine D2 receptorsVoxel-based analysisPriming bolusSensorimotor subdivisionsAmphetamine administrationMotor functionStriatal functionD2 receptorsIntravenous administrationStriatal subregionsVentral midbrainHealthy volunteersDopamine transmission
2002
Comparative Evaluation in Nonhuman Primates of Five PET Radiotracers for Imaging the Serotonin Transporters: [11C]McN 5652, [11C]ADAM, [11C]DASB, [11C]DAPA, and [11C]AFM
Huang Y, Hwang D, Narendran R, Sudo Y, Chatterjee R, Bae S, Mawlawi O, Kegeles L, Wilson A, Kung H, Laruelle M. Comparative Evaluation in Nonhuman Primates of Five PET Radiotracers for Imaging the Serotonin Transporters: [11C]McN 5652, [11C]ADAM, [11C]DASB, [11C]DAPA, and [11C]AFM. Cerebrovascular And Brain Metabolism Reviews 2002, 22: 1377-1398. DOI: 10.1097/00004647-200211000-00011.Peer-Reviewed Original ResearchPositron emission tomographySerotonin transporterSERT availabilitySlow brain kineticsNonspecific equilibrium partition coefficientN-dimethylVivo positron emission tomographyEquilibrium partition coefficientHigher free fractionKinetic uptakeRegional distribution volumesPartition coefficientsSuperior radiotracerBrain uptakeBrain kineticsOne-tissue compartment modelLimbic systemSERT imagingBrain regionsDistribution volumeEmission tomographyKinetic modelingNew radiotracersMeasurement of affinityPromising agent