2024
11C-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 synapsesAutismNovel 18F‑Labeled Benzimidazolone-Based Radioligands as Highly Selective Sigma‑2 Receptor Probes for Tumor Imaging
Wang J, Wang T, Mou T, Yang T, Gao X, An X, Hu B, Zhang J, Zhang X, Deuther-Conrad W, Huang Y, Jia H. Novel 18F‑Labeled Benzimidazolone-Based Radioligands as Highly Selective Sigma‑2 Receptor Probes for Tumor Imaging. Journal Of Medicinal Chemistry 2024, 67: 17392-17406. DOI: 10.1021/acs.jmedchem.4c01315.Peer-Reviewed Original ResearchSmall-animal PET/CTS2 receptorsAnimal PET/CTHigh subtype selectivityGlioma modelCo-administrationPET/CTLung cancerGlioma xenograftsBlocking studiesU87MG xenograftsA549 lung cancerCompound 4U87MG glioma xenograftsTumorTumor imagingReceptorsSubtype selectivityXenograftsRadiochemical yieldRadioligandSigma-2Active uptakeMolar activityU87MGValidation 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, jnumed.124.267419. PMID: 39299782, 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 alterationsClinical correlates of dopamine transporter availability in cross-sectional and longitudinal studies with [18F]FE-PE2I PET: independent validation with new insights
Honhar P, Sadabad F, Tinaz S, Gallezot J, Dias M, Naganawa M, Yang Y, Henry S, Hillmer A, Gao H, Najafzadeh S, Comley R, Nabulsi N, Huang Y, Finnema S, Carson R, Matuskey D. Clinical correlates of dopamine transporter availability in cross-sectional and longitudinal studies with [18F]FE-PE2I PET: independent validation with new insights. Brain Communications 2024, 6: fcae345. PMID: 39429243, PMCID: PMC11487911, DOI: 10.1093/braincomms/fcae345.Peer-Reviewed Original ResearchDAT availabilityMotor severitySubstantia nigraDopamine transporter availabilityClinical trials of Parkinson's diseaseParkinson's diseaseLongitudinal studyTracking longitudinal changesClinical correlatesVentral striatumTransporter availabilityNigrostriatal regionParkinson's disease patientsPutamenMotor severity scoresAssociated with increasesSubstantiaDATLongitudinal changesTremor scoreNegative associationNigraSubstantia nigra of Parkinson's disease patientsTremor severityPET biomarkersMicroglia-mediated neuroimmune suppression in PTSD is associated with anhedonia
Bonomi R, Hillmer A, Woodcock E, Bhatt S, Rusowicz A, Angarita G, Carson R, Davis M, Esterlis I, Nabulsi N, Huang Y, Krystal J, Pietrzak R, Cosgrove K. Microglia-mediated neuroimmune suppression in PTSD is associated with anhedonia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2406005121. PMID: 39172786, PMCID: PMC11363315, DOI: 10.1073/pnas.2406005121.Peer-Reviewed Original ResearchConceptsPTSD groupPrefrontal-limbic circuitsNeuroimmune responseAssociated with anhedoniaPosttraumatic stress disorderPositron emission tomography brain imagingTranslocator protein availabilityBrain immune functionAnhedonic symptomsStress disorderPeripheral immune dysfunctionPTSDGroup differencesSeverity of symptomsPsychiatric diseasesTranslocator proteinBrain imagingAdministration of lipopolysaccharideSymptomsMicroglial markersLPS-induced increaseCompared to controlsImmune functionSickness symptomsAnhedoniaNoninvasive 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 controlsPresynaptic density determined by SV2A PET is closely associated with postsynaptic metabotropic glutamate receptor 5 availability and independent of amyloid pathology in early cognitive impairment
Wang J, Huang Q, He K, Li J, Guo T, Yang Y, Lin Z, Li S, Vanderlinden G, Huang Y, Van Laere K, Guan Y, Guo Q, Ni R, Li B, Xie F. Presynaptic density determined by SV2A PET is closely associated with postsynaptic metabotropic glutamate receptor 5 availability and independent of amyloid pathology in early cognitive impairment. Alzheimer's & Dementia 2024, 20: 3876-3888. PMID: 38634334, PMCID: PMC11180932, DOI: 10.1002/alz.13817.Peer-Reviewed Original ResearchMGluR5 availabilityMedial temporal lobeSynaptic densityTemporal lobeHealthy controlsAlzheimer's diseaseMetabotropic glutamate receptor 5Glutamate receptor 5Synaptic lossIntegrative brain functionsCognitively impaired patientsEarly cognitive impairmentGlobal cognitionMGluR5 signalingMediation analysisPathophysiological mechanism of Alzheimer's diseaseBrain functionCognitive impairmentMGluR5CognitionImproving synaptic functionImpaired patientsSynaptic functionSynaptic transmissionAmyloid pathologyTau 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 participantsFirst-in-Human Study of 18F-SynVesT-2: An SV2A PET Imaging Probe with Fast Brain Kinetics and High Specific Binding
Drake L, Wu Y, Naganawa M, Asch R, Zheng C, Najafzadeh S, Pracitto R, Lindemann M, Li S, Ropchan J, Labaree D, Emery P, Dias M, Henry S, Nabulsi N, Matuskey D, Hillmer A, Gallezot J, Carson R, Cai Z, Huang Y. First-in-Human Study of 18F-SynVesT-2: An SV2A PET Imaging Probe with Fast Brain Kinetics and High Specific Binding. Journal Of Nuclear Medicine 2024, 65: jnumed.123.266470. PMID: 38360052, PMCID: PMC10924160, DOI: 10.2967/jnumed.123.266470.Peer-Reviewed Original ResearchFirst-in-human studyPlasma free fractionTime-activity curvesCentrum semiovaleNonhuman primate's resultsFirst-in-humanFree fractionNondisplaceable binding potentialRegional time-activity curvesLow nonspecific uptakeRegional distribution volumesHigh-resolution research tomograph scannerTest-retest reproducibilityCerebral blood flowSynaptic vesicle glycoprotein 2AHealthy volunteersArterial input functionNonspecific uptakePET imaging probeDistribution volumeSynapse densityIndividual MR imagesHighest specific bindingMR imagingPET imagingIntense exercise increases dopamine transporter and neuromelanin concentrations in the substantia nigra in Parkinson’s disease
de Laat B, Hoye J, Stanley G, Hespeler M, Ligi J, Mohan V, Wooten D, Zhang X, Nguyen T, Key J, Colonna G, Huang Y, Nabulsi N, Patel A, Matuskey D, Morris E, Tinaz S. Intense exercise increases dopamine transporter and neuromelanin concentrations in the substantia nigra in Parkinson’s disease. Npj Parkinson's Disease 2024, 10: 34. PMID: 38336768, PMCID: PMC10858031, DOI: 10.1038/s41531-024-00641-1.Peer-Reviewed Original ResearchDopamine transporterSubstantia nigraDopaminergic neuronsDopamine transporter availabilityNeuroprotective effects of exerciseDopaminergic systemClinical progression of PDEarly PDSubstantiaNeuromelanin contentNigraLoss of dopaminergic neuronsEffects of exerciseNM-MRIDopamineSystem of patientsProgressive loss of dopaminergic neuronsParkinson's diseaseClinical progressionProgression of PDNeuroprotective effectsClinical trialsIntensity exercisePET imagingProgressive lossThe associations between synaptic density and “A/T/N” biomarkers in Alzheimer’s disease: An 18F-SynVesT-1 PET/MR study
Li J, Huang Q, Qi N, He K, Li S, Huang L, Pan F, Ren S, Hua F, Huang Y, Guan Y, Guo Q, Zhao J, Xie F. The associations between synaptic density and “A/T/N” biomarkers in Alzheimer’s disease: An 18F-SynVesT-1 PET/MR study. Cerebrovascular And Brain Metabolism Reviews 2024, 44: 1199-1207. PMID: 38295871, PMCID: PMC11179616, DOI: 10.1177/0271678x241230733.Peer-Reviewed Original ResearchSynaptic densityF-FDG PET/CTInvestigate synaptic densityFDG uptakeF-FDGCognitive impairmentClinical syndromeCI groupPlasma testingPET/MR studiesPathological changesSubgroups of individualsSynaptic density lossDensity lossBiomarkersAlzheimer's clinical syndromePatientsPET/MRHippocampusAlzheimer's diseaseHippocampal volumeParahippocampal gyrusCI+ groupDiseaseSynapse lossA 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
PET Imaging of Rho‐Associated Protein Kinase 2 in A Mouse Model of Alzheimer’s Disease
Zheng C, Nicholson L, Chen B, Toyonaga T, Liu M, Strittmatter S, Carson R, Huang Y, Cai Z. PET Imaging of Rho‐Associated Protein Kinase 2 in A Mouse Model of Alzheimer’s Disease. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.081695.Peer-Reviewed Original ResearchAPP/PS1 micePS1 miceWT miceCentral nervous systemTime-activity curvesAlzheimer's diseaseAPP/PS1 transgenic miceAPP/PS1 transgenic AD miceMouse brainAge-matched WT controlsPS1 transgenic miceAPP/PS1Transgenic AD miceDynamic PET imaging dataROCK2 protein expressionAD drug discoveryHigh tracer uptakeMin post injectionPET imaging resultsExpression levelsReference tissue model 2PET imaging dataProtein expression levelsAD miceRegional time-activity curvesEvaluation of a First PET Tracer Suitable for Imaging the Sigma‑2 Receptor in the Brain of Nonhuman Primates
Alluri S, Zheng M, Holden D, Zhang Y, Zhang L, Felchner Z, Li S, Ropchan J, Carson R, Jia H, Huang Y. Evaluation of a First PET Tracer Suitable for Imaging the Sigma‑2 Receptor in the Brain of Nonhuman Primates. Molecular Pharmaceutics 2023, 21: 194-200. PMID: 38013422, DOI: 10.1021/acs.molpharmaceut.3c00750.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseLimited brain uptakeNonhuman primate brainCentral nervous systemPotential therapeutic targetPositron emission tomography (PET) imagingEmission Tomography ImagingTransmembrane protein 97Sigma-2 receptorsFirst PET tracerBrain penetrantBrain uptakeTherapeutic targetNervous systemPrimate brainNeurological disordersPET tracersNonhuman primatesTomography imagingProtein 97CancerDiseaseBrainCell typesReceptorsThe regional pattern of age-related synaptic loss in the human brain differs from gray matter volume loss: in vivo PET measurement with [11C]UCB-J
Toyonaga T, Khattar N, Wu Y, Lu Y, Naganawa M, Gallezot J, Matuskey D, Mecca A, Pittman B, Dias M, Nabulsi N, Finnema S, Chen M, Arnsten A, Radhakrishnan R, Skosnik P, D’Souza D, Esterlis I, Huang Y, van Dyck C, Carson R. The regional pattern of age-related synaptic loss in the human brain differs from gray matter volume loss: in vivo PET measurement with [11C]UCB-J. European Journal Of Nuclear Medicine And Molecular Imaging 2023, 51: 1012-1022. PMID: 37955791, DOI: 10.1007/s00259-023-06487-8.Peer-Reviewed Original ResearchSynaptic densityAge-related decreaseMagnetic resonance imagingBlood flowAge-related synaptic lossGray matter volume lossSynaptic density lossPositron emission tomography (PET) ligandSynaptic vesicle glycoprotein 2AVivo PET measurementsMedial occipital cortexGray matter volumeAge-related neurodegenerationGray matter regionsCognitive normal subjectsAge-related changesSynaptic lossNerve terminalsWide age rangeOccipital cortexTomography ligandNormal subjectsGM volumeAge-related functional lossesMatter volumeDevelopment of a Highly Specific 18F‑Labeled Radioligand for Imaging of the Sigma‑2 Receptor in Brain Tumors
Wang T, Wang J, Chen L, Zhang X, Mou T, An X, Zhang J, Zhang X, Deuther-Conrad W, Huang Y, Jia H. Development of a Highly Specific 18F‑Labeled Radioligand for Imaging of the Sigma‑2 Receptor in Brain Tumors. Journal Of Medicinal Chemistry 2023, 66: 12840-12857. PMID: 37704582, DOI: 10.1021/acs.jmedchem.3c00735.Peer-Reviewed Original ResearchMicro-PET/CT imagingSigma-2 receptorsTumor uptakeCT imagingClear tumor visualizationGlioma xenograft modelU87MG glioma xenograftsHigh subtype selectivityHigh tumor uptakeHigh specific bindingGlioma xenograftsBrain tumorsXenograft modelTumor visualizationSubtype selectivityReceptorsTumorsRadioligandSpecific bindingGBq/ImagingRadiochemical purityNanomolar affinityAssessment 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 impairmentDisease