2021
Brain opioid segments and striatal patterns of dopamine release induced by naloxone and morphine
Shokri‐Kojori E, Naganawa M, Ramchandani VA, Wong DF, Wang G, Volkow ND. Brain opioid segments and striatal patterns of dopamine release induced by naloxone and morphine. Human Brain Mapping 2021, 43: 1419-1430. PMID: 34873784, PMCID: PMC8837588, DOI: 10.1002/hbm.25733.Peer-Reviewed Original ResearchConceptsOpioid receptor availabilityStriatal DA releaseDA releaseOpioid receptorsReceptor availabilityDopamine releaseStriatal dopamine releaseOpioid use disorderBrain-wide distributionInverse associationHealthy controlsStriatal distributionClinical studiesStriatal patternUse disordersSubcortical regionsVentral striatumGray matter segmentsReceptorsNaloxoneMorphineStriatumDA targetsRelease patternReleaseComparison 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 patternPET Imaging Estimates of Regional Acetylcholine Concentration Variation in Living Human Brain
Smart K, Naganawa M, Baldassarri SR, Nabulsi N, Ropchan J, Najafzadeh S, Gao H, Navarro A, Barth V, Esterlis I, Cosgrove KP, Huang Y, Carson RE, Hillmer AT. PET Imaging Estimates of Regional Acetylcholine Concentration Variation in Living Human Brain. Cerebral Cortex 2021, 31: 2787-2798. PMID: 33442731, PMCID: PMC8355478, DOI: 10.1093/cercor/bhaa387.Peer-Reviewed Original ResearchConceptsACh concentrationHuman volunteersHigh ACh concentrationsMuscarinic antagonist scopolamineHealthy human volunteersHuman brainCholinergic receptorsNicotine challengeAntagonist scopolaminePreclinical studiesStriatal regionsPET scansEndogenous neurotransmittersNeuropsychiatric diseasesNonhuman primatesWhole-brain imagesDrug occupancyNicotinic ligandsClinical populationsBrainAcetylcholineDistinct functional rolesStriatumVolunteersFunctional role
2020
Reduced 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 zoneFirst-in-Human Assessment of 11C-LSN3172176, an M1 Muscarinic Acetylcholine Receptor PET Radiotracer
Naganawa M, Nabulsi N, Henry S, Matuskey D, Lin SF, Slieker L, Schwarz AJ, Kant N, Jesudason C, Ruley K, Navarro A, Gao H, Ropchan J, Labaree D, Carson RE, Huang Y. First-in-Human Assessment of 11C-LSN3172176, an M1 Muscarinic Acetylcholine Receptor PET Radiotracer. Journal Of Nuclear Medicine 2020, 62: 553-560. PMID: 32859711, PMCID: PMC8049371, DOI: 10.2967/jnumed.120.246967.Peer-Reviewed Original ResearchConceptsSimplified reference tissue modelM1 receptorsHealthy subjectsMuscarinic acetylcholine receptor subtype M1Distribution volumePET radiotracersAbsolute test-retest variabilityExcellent test-retest reproducibilityReference tissue model 2Total distribution volumeSuitable reference regionTest-retest reproducibilityTest-retest variabilityReference regionTest-retest protocolNondisplaceable distribution volumeReference tissue modelTest-retest studySubtypes M1Preclinical studiesRegional time-activity curvesAcetylcholine concentrationHuman studiesReceptor occupancyTime-activity curvesFirst-in-Human Evaluation of 18F-SynVesT-1, a Radioligand for PET Imaging of Synaptic Vesicle Glycoprotein 2A
Naganawa M, Li S, Nabulsi N, Henry S, Zheng MQ, Pracitto R, Cai Z, Gao H, Kapinos M, Labaree D, Matuskey D, Huang Y, Carson RE. First-in-Human Evaluation of 18F-SynVesT-1, a Radioligand for PET Imaging of Synaptic Vesicle Glycoprotein 2A. Journal Of Nuclear Medicine 2020, 62: 561-567. PMID: 32859701, PMCID: PMC8049363, DOI: 10.2967/jnumed.120.249144.Peer-Reviewed Original ResearchConceptsC-UCBSynaptic densityRegional time-activity curvesTime-activity curvesDistribution volumeMetabolite-corrected arterial input functionPET imagingMultilinear analysis 1Synaptic vesicle glycoprotein 2AAntiepileptic drug levetiracetamTotal distribution volumeNondisplaceable distribution volumeCentrum semiovaleBlocking doseHealthy volunteersHuman studiesDrug levetiracetamLassen plotNeuropsychiatric disordersPET radioligandArterial input functionNonhuman primatesLevetiracetamReference regionRadioligandSimplified Quantification of 11C-UCB-J PET Evaluated in a Large Human Cohort
Naganawa M, Gallezot JD, Finnema SJ, Matuskey D, Mecca A, Nabulsi NB, Labaree D, Ropchan J, Malison RT, D'Souza DC, Esterlis I, Detyniecki K, van Dyck CH, Huang Y, Carson RE. Simplified Quantification of 11C-UCB-J PET Evaluated in a Large Human Cohort. Journal Of Nuclear Medicine 2020, 62: 418-421. PMID: 32646875, PMCID: PMC8049341, DOI: 10.2967/jnumed.120.243949.Peer-Reviewed Original ResearchIn 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 correlatesKinetic Modeling and Test–Retest Reproducibility of 11C-EKAP and 11C-FEKAP, Novel Agonist Radiotracers for PET Imaging of the κ-Opioid Receptor in Humans
Naganawa M, Li S, Nabulsi N, Lin SF, Labaree D, Ropchan J, Gao H, Mei M, Henry S, Matuskey D, Carson RE, Huang Y. Kinetic Modeling and Test–Retest Reproducibility of 11C-EKAP and 11C-FEKAP, Novel Agonist Radiotracers for PET Imaging of the κ-Opioid Receptor in Humans. Journal Of Nuclear Medicine 2020, 61: 1636-1642. PMID: 32169917, PMCID: PMC9364890, DOI: 10.2967/jnumed.119.227694.Peer-Reviewed Original ResearchSynaptic 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 system
2019
PET Imaging of Pancreatic Dopamine D2 and D3 Receptor Density with 11C-(+)-PHNO in Type 1 Diabetes
Bini J, Sanchez-Rangel E, Gallezot JD, Naganawa M, Nabulsi N, Lim K, Najafzadeh S, Shirali A, Ropchan J, Matuskey D, Huang Y, Herold K, Harris PE, Sherwin RS, Carson RE, Cline GW. PET Imaging of Pancreatic Dopamine D2 and D3 Receptor Density with 11C-(+)-PHNO in Type 1 Diabetes. Journal Of Nuclear Medicine 2019, 61: 570-576. PMID: 31601695, PMCID: PMC7198375, DOI: 10.2967/jnumed.119.234013.Peer-Reviewed Original ResearchConceptsT1DM individualsHealthy controlsDopamine DOutcome measuresAcute C-peptide responseSUVR-1Type 1 diabetes mellitusPET/CT scanningDuration of diabetesMaximal glycemic potentiationC-peptide responseClinical outcome measuresInsulin secretory capacityRoutine clinical measuresD3 receptor densityΒ-cell functionC-peptide releaseQuantitative PET measuresΒ-cell massDynamic PET scansQuantitative outcome measuresAgonist PET radioligandDiabetes mellitusReceptor agonistInsulin antibodiesAssessment 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 ResearchIn Vivo Synaptic Density Imaging with 11C-UCB-J Detects Treatment Effects of Saracatinib in a Mouse Model of Alzheimer Disease
Toyonaga T, Smith LM, Finnema SJ, Gallezot JD, Naganawa M, Bini J, Mulnix T, Cai Z, Ropchan J, Huang Y, Strittmatter SM, Carson RE. In Vivo Synaptic Density Imaging with 11C-UCB-J Detects Treatment Effects of Saracatinib in a Mouse Model of Alzheimer Disease. Journal Of Nuclear Medicine 2019, 60: 1780-1786. PMID: 31101744, PMCID: PMC6894376, DOI: 10.2967/jnumed.118.223867.Peer-Reviewed Original ResearchConceptsAPP/PS1 micePS1 miceAlzheimer's diseaseWT miceSynaptic densityC-UCBDrug washoutTreatment effectsPresenilin 1 (PS1) double transgenic miceHippocampal synaptic densityAPP/PS1Double transgenic miceEnd of treatmentWild-type miceAmyloid precursor proteinEarly Alzheimer's diseaseSignificant differencesSUVR-1New PET tracersMild cognitive impairmentAD miceSynaptic deficitsOral gavageAD treatmentHealthy subjectsLower 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 evidenceSymptomsDepressionSeverityDisordersAlterationsSocial 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 volumesA 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
Assessing 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 measuresImproved discrimination between benign and malignant LDCT screening-detected lung nodules with dynamic over static 18F-FDG PET as a function of injected dose
Ye Q, Wu J, Lu Y, Naganawa M, Gallezot JD, Ma T, Liu Y, Tanoue L, Detterbeck F, Blasberg J, Chen MK, Casey M, Carson RE, Liu C. Improved discrimination between benign and malignant LDCT screening-detected lung nodules with dynamic over static 18F-FDG PET as a function of injected dose. Physics In Medicine And Biology 2018, 63: 175015. PMID: 30095083, PMCID: PMC6158045, DOI: 10.1088/1361-6560/aad97f.Peer-Reviewed Original ResearchConceptsPopulation-based input functionStandardized uptake valueImage-derived input functionLung nodulesClinical trialsTime-activity curvesLow-dose computed tomography (LDCT) screeningLung cancer mortality ratesIndeterminate lung nodulesComputed Tomography ScreeningF-FDG PETCancer mortality ratesStatic PET acquisitionVirtual clinical trialsScan durationTomography screeningFDG injectionPET scansMortality rateUptake valueAccurate diagnosisMalignant lung nodulesROC analysisPatient dataMalignant nodulesDecreased VMAT2 in the pancreas of humans with type 2 diabetes mellitus measured in vivo by PET imaging
Cline GW, Naganawa M, Chen L, Chidsey K, Carvajal-Gonzalez S, Pawlak S, Rossulek M, Zhang Y, Bini J, McCarthy TJ, Carson RE, Calle RA. Decreased VMAT2 in the pancreas of humans with type 2 diabetes mellitus measured in vivo by PET imaging. Diabetologia 2018, 61: 2598-2607. PMID: 29721633, DOI: 10.1007/s00125-018-4624-0.Peer-Reviewed Original ResearchConceptsVesicular monoamine transporter type 2Type 2 diabetesBeta-cell massHealthy obese volunteersStandardised uptake value ratioBeta-cell functionTest-retest variabilityPancreas headTracer uptakeSUVR-1Type 2 diabetes mellitusType 2 diabetic participantsBeta-cell capacityConclusions/interpretationTheC-peptide AUCImpaired glucose toleranceType 2 diabetes pathophysiologyCell functionDeficient insulin secretionAcute insulin responsePancreas of humansUptake value ratioC-peptide releasePancreatic polypeptide cellsTransporter type 2Evaluation of Pancreatic VMAT2 Binding with Active and Inactive Enantiomers of [18F]FP-DTBZ in Healthy Subjects and Patients with Type 1 Diabetes
Naganawa M, Lim K, Nabulsi NB, Lin SF, Labaree D, Ropchan J, Herold KC, Huang Y, Harris P, Ichise M, Cline GW, Carson RE. Evaluation of Pancreatic VMAT2 Binding with Active and Inactive Enantiomers of [18F]FP-DTBZ in Healthy Subjects and Patients with Type 1 Diabetes. Molecular Imaging And Biology 2018, 20: 835-845. PMID: 29468404, PMCID: PMC6533199, DOI: 10.1007/s11307-018-1170-6.Peer-Reviewed Original ResearchConceptsVesicular monoamine transporter type 2Non-displaceable uptakeHealthy controlsSUV ratioType 1 diabetes mellitus groupInactive enantiomerDiabetes mellitus groupBeta-cell massFirst human studyGroup differencesPositron emission tomography (PET) radiotracerTransporter type 2Mellitus groupVT valuesSignificant group differencesT1DM patientsRenal cortexHealthy subjectsPurposePrevious studiesHuman studiesUptake valueType 2Separate daysDistribution volumeReference SUV