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 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 timeBPNDSemiovaleSynaptic loss and its association with symptom severity in Parkinson’s disease
Holmes S, Honhar P, Tinaz S, Naganawa M, Hilmer A, Gallezot J, Dias M, Yang Y, Toyonaga T, Esterlis I, Mecca A, Van Dyck C, Henry S, Ropchan J, Nabulsi N, Louis E, Comley R, Finnema S, Carson R, Matuskey D. Synaptic loss and its association with symptom severity in Parkinson’s disease. Npj Parkinson's Disease 2024, 10: 42. PMID: 38402233, PMCID: PMC10894197, DOI: 10.1038/s41531-024-00655-9.Peer-Reviewed Original ResearchSynaptic density lossPositron emission tomographyBinds to synaptic vesicle glycoprotein 2AAssociated with symptom severityParkinson's diseaseHigh-resolution positron emission tomographySynaptic vesicle glycoprotein 2ADuration of illnessPositron emission tomography scanBrain perfusionIllness durationSymptom severitySeverity of symptomsHC groupSubstantia nigraSynaptic densityLiving brainPD individualsClinical insightsDensity lossPD patientsEmission tomographyBrainSynaptic lossSynapse loss
2022
Imaging the effect of ketamine on synaptic density (SV2A) in the living brain
Holmes SE, Finnema SJ, Naganawa M, DellaGioia N, Holden D, Fowles K, Davis M, Ropchan J, Emory P, Ye Y, Nabulsi N, Matuskey D, Angarita GA, Pietrzak RH, Duman RS, Sanacora G, Krystal JH, Carson RE, Esterlis I. Imaging the effect of ketamine on synaptic density (SV2A) in the living brain. Molecular Psychiatry 2022, 27: 2273-2281. PMID: 35165397, PMCID: PMC9133063, DOI: 10.1038/s41380-022-01465-2.Peer-Reviewed Original ResearchConceptsKetamine's therapeutic effectsMajor depressive disorderTherapeutic effectPositron emission tomographyPosttraumatic stress disorderHealthy controlsSynaptic connectionsSynaptic vesicle protein 2APost-synaptic mechanismsEffects of ketamineDiscovery of ketamineNon-human primatesAntidepressant effectsDepressive disorderSingle administrationSynaptic densityPsychiatric disordersDepression severityKetamineEmission tomographyTerminal densityLiving brainStress disorderRobust reductionDissociative symptoms
2021
Association 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
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 proteinsPreliminary in vivo evidence of lower hippocampal synaptic density in cannabis use disorder
D’Souza D, Radhakrishnan R, Naganawa M, Ganesh S, Nabulsi N, Najafzadeh S, Ropchan J, Ranganathan M, Cortes-Briones J, Huang Y, Carson RE, Skosnik P. Preliminary in vivo evidence of lower hippocampal synaptic density in cannabis use disorder. Molecular Psychiatry 2020, 26: 3192-3200. PMID: 32973170, DOI: 10.1038/s41380-020-00891-4.Peer-Reviewed Original ResearchConceptsHippocampal synaptic densityCannabis use disorderHealthy controlsSynaptic densityPositron emission tomographyUse disordersDSM-5 cannabis use disorderVivo evidenceAdministration of cannabinoidsHippocampal synaptic integrityVerbal memory taskSynaptic vesicle glycoprotein 2AHuman cannabis usersEffects of cannabisWarrants further studyPlasma input functionMemory taskCentrum semiovaleAdult rodentsOne-tissue compartment modelSynaptic integrityHippocampal functionCannabis misuseArterial samplingEmission tomographyReduced 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 zone
2019
Lower 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 evidenceSymptomsDepressionSeverityDisordersAlterationsParametric Imaging With PET and SPECT
Gallezot J, Lu Y, Naganawa M, Carson R. Parametric Imaging With PET and SPECT. IEEE Transactions On Radiation And Plasma Medical Sciences 2019, 4: 1-23. DOI: 10.1109/trpms.2019.2908633.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMolecular imaging modalitiesConcentration imagesPositron emission tomographyPhoton emissionSubject motionSocial status and demographic effects of the kappa opioid receptor: a PET imaging study with a novel agonist radiotracer in healthy volunteers
Matuskey D, Dias M, Naganawa M, Pittman B, Henry S, Li S, Gao H, Ropchan J, Nabulsi N, Carson RE, Huang Y. Social status and demographic effects of the kappa opioid receptor: a PET imaging study with a novel agonist radiotracer in healthy volunteers. Neuropsychopharmacology 2019, 44: 1714-1719. PMID: 30928993, PMCID: PMC6785144, DOI: 10.1038/s41386-019-0379-7.Peer-Reviewed Original ResearchConceptsBody mass indexKappa-opioid receptorsPositron emission tomographyAgonist radiotracerKOR systemOpioid receptorsTime-activity curvesBarratt Simplified MeasureAnterior cingulate cortexArterial blood samplingMultilinear analysis-1 (MA1) methodPET imaging studiesKOR levelsMass indexPreclinical modelsFrontal cortexHealthy volunteersRegional time-activity curvesBlood samplingPET scansCingulate cortexImaging studiesEmission tomographyVentral striatumRegional volumes
2018
Dose-Related Target Occupancy and Effects on Circuitry, Behavior, and Neuroplasticity of the Glycine Transporter-1 Inhibitor PF-03463275 in Healthy and Schizophrenia Subjects
D’Souza D, Carson RE, Driesen N, Johannesen J, Ranganathan M, Krystal JH, Ahn K, Bielen K, Carbuto M, Deaso E, D’Souza D, Ranganathan M, Naganawa M, Ranganathan M, D’Souza D, Nabulsi N, Zheng M, Lin S, Huang Y, Carson R, Driesen N, Ahn K, Morgan P, Suckow R, He G, McCarthy G, Krystal J, Johannesen J, Kenney J, Gelernter J, Gueorguieva R, Pittman B. Dose-Related Target Occupancy and Effects on Circuitry, Behavior, and Neuroplasticity of the Glycine Transporter-1 Inhibitor PF-03463275 in Healthy and Schizophrenia Subjects. Biological Psychiatry 2018, 84: 413-421. PMID: 29499855, PMCID: PMC6068006, DOI: 10.1016/j.biopsych.2017.12.019.Peer-Reviewed Original ResearchMeSH KeywordsAdultAzabicyclo CompoundsBrainCognitive DysfunctionDose-Response Relationship, DrugDouble-Blind MethodFemaleGlycine Plasma Membrane Transport ProteinsHumansImidazolesKetamineLong-Term PotentiationMagnetic Resonance ImagingMaleMemory, Short-TermMiddle AgedPositron-Emission TomographySchizophreniaYoung AdultConceptsHealthy control subjectsLong-term potentiationSchizophrenia patientsControl subjectsCognitive impairmentClinical trialsGlyT1 occupancyN-methyl-D-aspartate receptor functionGlycine transporter-1 inhibitorKetamine-induced disruptionKetamine-induced effectsFunctional magnetic resonance imagingMagnetic resonance imagingPositron emission tomographyMemory-related activationF-MKSubstudy 1Schizophrenia subjectsResonance imagingReceptor functionCortical regionsEmission tomographyTarget engagementPotentiationSchizophrenia
2016
Evaluation of pancreatic VMAT2 binding with active and inactive enantiomers of 18F-FP-DTBZ in baboons
Naganawa M, Lin SF, Lim K, Labaree D, Ropchan J, Harris P, Huang Y, Ichise M, Carson RE, Cline GW. Evaluation of pancreatic VMAT2 binding with active and inactive enantiomers of 18F-FP-DTBZ in baboons. Nuclear Medicine And Biology 2016, 43: 743-751. PMID: 27673755, PMCID: PMC5248981, DOI: 10.1016/j.nucmedbio.2016.08.018.Peer-Reviewed Original ResearchConceptsRenal cortexPositron emission tomographyInactive enantiomerRadiometabolite fractionΒ-cell massHuman β-cell massNon-displaceable bindingEx vivo studyF-FPLow inter-subject variabilityPET scansDTBZ bindingSpleen uptakeDistribution volumeEmission tomographySpleenPancreasDTBZCortexVivo studiesTissue samplesInter-subject variabilityHigh uptakePET signalRadiometabolites
2015
Receptor Occupancy of the κ-Opioid Antagonist LY2456302 Measured with Positron Emission Tomography and the Novel Radiotracer 11C-LY2795050
Naganawa M, Dickinson GL, Zheng MQ, Henry S, Vandenhende F, Witcher J, Bell R, Nabulsi N, Lin SF, Ropchan J, Neumeister A, Ranganathan M, Tauscher J, Huang Y, Carson RE. Receptor Occupancy of the κ-Opioid Antagonist LY2456302 Measured with Positron Emission Tomography and the Novel Radiotracer 11C-LY2795050. Journal Of Pharmacology And Experimental Therapeutics 2015, 356: 260-266. PMID: 26628406, PMCID: PMC4727157, DOI: 10.1124/jpet.115.229278.Peer-Reviewed Original ResearchConceptsHours postdosePositron emission tomographyReceptor occupancyEmission tomographySerious adverse eventsSingle oral dosesImportant therapeutic roleΚ-opioid receptorsSubstance abuse disordersFurther clinical testingHealthy human subjectsMultilinear analysis-1 (MA1) methodAntagonist radiotracersAdverse eventsOral dosesBrain penetrationTherapeutic rolePlasma concentrationsAbuse disordersEthanol consumptionLY2456302Clinical testingNovel radiotracersAlcohol dependenceDistribution volume
2013
Tracer Kinetic Modeling of [11C]AFM, a New PET Imaging Agent for the Serotonin Transporter
Naganawa M, Nabulsi N, Planeta B, Gallezot JD, Lin SF, Najafzadeh S, Williams W, Ropchan J, Labaree D, Neumeister A, Huang Y, Carson RE. Tracer Kinetic Modeling of [11C]AFM, a New PET Imaging Agent for the Serotonin Transporter. Cerebrovascular And Brain Metabolism Reviews 2013, 33: 1886-1896. PMID: 23921898, PMCID: PMC3851894, DOI: 10.1038/jcbfm.2013.134.Peer-Reviewed Original ResearchConceptsPositron emission tomographySerotonin transporterReference tissue modelArterial input functionOne-tissue modelMultilinear reference tissue modelNew PET imaging agentTwo-tissue modelPET imaging agentHealthy human brainSuitable PET radioligandNew positron emission tomographySERT densityRegional time-activity curvesTime-activity curvesEmission tomography dataRegional bindingEmission tomographyPET radioligandRoutine useInterest analysisNoninvasive methodPositron emission tomography dataImaging agentHuman brain
2011
Adenosine A2A Receptors Measured with [11C]TMSX PET in the Striata of Parkinson's Disease Patients
Mishina M, Ishiwata K, Naganawa M, Kimura Y, Kitamura S, Suzuki M, Hashimoto M, Ishibashi K, Oda K, Sakata M, Hamamoto M, Kobayashi S, Katayama Y, Ishii K. Adenosine A2A Receptors Measured with [11C]TMSX PET in the Striata of Parkinson's Disease Patients. PLOS ONE 2011, 6: e17338. PMID: 21386999, PMCID: PMC3046146, DOI: 10.1371/journal.pone.0017338.Peer-Reviewed Original ResearchConceptsDrug-naïve patientsDrug-naïve PD patientsPositron emission tomographyPD patientsParkinson's diseaseAntiparkinsonian therapyControl subjectsAffected sideDisease patientsCaudate nucleusParkinson's disease patientsElderly control subjectsNormal control subjectsSelective A2AR antagonistAdenosine A2A receptorsDistribution volume ratioMild dyskinesiaA2AR antagonistDopaminergic systemBilateral putamenPET scansPatientsA2A receptorsNovel treatmentsPutamen
2007
Distribution volume as an alternative to the binding potential for sigma1 receptor imaging
Kimura Y, Naganawa M, Sakata M, Ishikawa M, Mishina M, Oda K, Ishii K, Ishiwata K. Distribution volume as an alternative to the binding potential for sigma1 receptor imaging. Annals Of Nuclear Medicine 2007, 21: 533-535. PMID: 18030587, DOI: 10.1007/s12149-007-0063-6.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnatomy, RegionalBrainBrain MappingCarbon RadioisotopesData Interpretation, StatisticalFemaleHumansImage Processing, Computer-AssistedMaleMiddle AgedNonlinear DynamicsPiperazinesPositron-Emission TomographyRadioligand AssayRadiopharmaceuticalsReceptors, sigmaReference StandardsConceptsPositron emission tomographyDistribution volumeTotal distribution volumeReference regionReceptor densityClinical investigationReceptor imagingSigma1 receptorsEmission tomographyAppropriate reference regionReceptorsTarget receptorsPhysiological situationsNeuroreceptor mappingHigh affinityImagingDVTDiseaseRadioligandBrainEvaluation of distribution of adenosine A2A receptors in normal human brain measured with [11C]TMSX PET
Mishina M, Ishiwata K, Kimura Y, Naganawa M, Oda K, Kobayashi S, Katayama Y, Ishii K. Evaluation of distribution of adenosine A2A receptors in normal human brain measured with [11C]TMSX PET. Synapse 2007, 61: 778-784. PMID: 17568431, DOI: 10.1002/syn.20423.Peer-Reviewed Original ResearchConceptsPositron emission tomographyPosterior putamenCaudate nucleusFrontal lobeHuman brainPromising PET ligandSelective A2AR antagonistNormal male subjectsMetabolite-corrected plasmaPosterior cingulate gyrusAdenosine A2A receptorsNormal human brainCerebral cortexA2AR antagonistCingulate gyrusArterial bloodOccipital lobeParkinson's diseaseTemporal lobePET scansA2A receptorsThree-compartment modelParietal lobePET ligandMale subjectsMapping of human cerebral sigma1 receptors using positron emission tomography and [11C]SA4503
Sakata M, Kimura Y, Naganawa M, Oda K, Ishii K, Chihara K, Ishiwata K. Mapping of human cerebral sigma1 receptors using positron emission tomography and [11C]SA4503. NeuroImage 2007, 35: 1-8. PMID: 17240168, DOI: 10.1016/j.neuroimage.2006.11.055.Peer-Reviewed Original ResearchMeSH KeywordsAdultBiotransformationBrainBrain ChemistryBrain MappingChromatography, High Pressure LiquidData Interpretation, StatisticalDopamine AntagonistsHaloperidolHumansImage Processing, Computer-AssistedMaleNonlinear DynamicsPiperazinesPositron-Emission TomographyRadioligand AssayRadiopharmaceuticalsReceptors, sigmaConceptsTotal distribution volumePositron emission tomographyEmission tomographyMetabolite correctionHealthy male subjectsSigma receptor antagonistLogan plotHuman brainPlasma input functionReceptor antagonistOral administrationClinical studiesPET scansThree-compartment modelPartial blockadePsychiatric diseasesMale subjectsSigma1RSigma1 receptorsBaseline measurementsDistribution volumeTwo-tissueHaloperidolBrainReceptors
2006
A feasibility study of [11C]SA4503-PET for evaluating sigma1 receptor occupancy by neuroleptics: The binding of haloperidol to sigma1 and dopamine D2-like receptors
Ishiwata K, Oda K, Sakata M, Kimura Y, Kawamura K, Oda K, Sasaki T, Naganawa M, Chihara K, Okubo Y, Ishii K. A feasibility study of [11C]SA4503-PET for evaluating sigma1 receptor occupancy by neuroleptics: The binding of haloperidol to sigma1 and dopamine D2-like receptors. Annals Of Nuclear Medicine 2006, 20: 569-573. PMID: 17134027, DOI: 10.1007/bf03026824.Peer-Reviewed Original ResearchConceptsReceptor occupancy ratesPositron emission tomographyDopamine D2-like receptorsD2-like receptorsHealthy male subjectsNon-selective antagonistPET scansReceptor occupancyHaloperidolMale subjectsBaseline measurementsPeroral administrationEmission tomographyBinding of haloperidolNeurolepticsAdministrationReceptorsPutamenCaudateDrugsDaysOccupancy rateAntagonistFeasibility study