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 patternReleasePET 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 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 regionRadioligandFirst-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 curvesKinetic 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 Research
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 ResearchLower 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 volumes
2018
Evaluation 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 SUVDose-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 engagementPotentiationSchizophreniaEvaluation of PET Brain Radioligands for Imaging Pancreatic β-Cell Mass: Potential Utility of 11C-(+)-PHNO
Bini J, Naganawa M, Nabulsi N, Huang Y, Ropchan J, Lim K, Najafzadeh S, Herold KC, Cline GW, Carson RE. Evaluation of PET Brain Radioligands for Imaging Pancreatic β-Cell Mass: Potential Utility of 11C-(+)-PHNO. Journal Of Nuclear Medicine 2018, 59: 1249-1254. PMID: 29371405, PMCID: PMC6071501, DOI: 10.2967/jnumed.117.197285.Peer-Reviewed Original ResearchConceptsT1DM subjectsΒ-cell massHealthy controlsΒ-cellsAbdominal organsType 1 diabetes mellitusC-peptide levelsHealthy control subjectsPancreatic β-cell massDeficient insulin secretionReceptor agonist radioligandPET/CTIslets of LangerhansDynamic PET/CTCommon cellular receptorPancreatic bindingDiabetes mellitusDiabetic subjectsControl subjectsNeurologic tissueC-peptideInsulin secretionMean SUVAgonist radioligandDiabetes therapy
2016
Event-by-Event Continuous Respiratory Motion Correction for Dynamic PET Imaging
Yu Y, Chan C, Ma T, Liu Y, Gallezot JD, Naganawa M, Kelada OJ, Germino M, Sinusas AJ, Carson RE, Liu C. Event-by-Event Continuous Respiratory Motion Correction for Dynamic PET Imaging. Journal Of Nuclear Medicine 2016, 57: 1084-1090. PMID: 26912437, DOI: 10.2967/jnumed.115.167676.Peer-Reviewed Original Research
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 volumeTest–Retest Reproducibility of Binding Parameters in Humans with 11C-LY2795050, an Antagonist PET Radiotracer for the κ Opioid Receptor
Naganawa M, Zheng MQ, Henry S, Nabulsi N, Lin SF, Ropchan J, Labaree D, Najafzadeh S, Kapinos M, Tauscher J, Neumeister A, Carson RE, Huang Y. Test–Retest Reproducibility of Binding Parameters in Humans with 11C-LY2795050, an Antagonist PET Radiotracer for the κ Opioid Receptor. Journal Of Nuclear Medicine 2015, 56: 243-248. PMID: 25593119, PMCID: PMC4322754, DOI: 10.2967/jnumed.114.147975.Peer-Reviewed Original ResearchConceptsTest-retest variabilityOpioid receptorsOutcome measuresAbsolute test-retest variabilityMultilinear analysis 1Healthy human subjectsSuitable reference regionTest-retest reproducibilityIntraclass correlation coefficientAntagonist radiotracersHealthy subjectsLY2795050PET scansBrain regionsDistribution volumePET radioligandTest-retest performancePET studiesArterial input functionPET radiotracersHuman subjectsReference regionReceptorsVT valuesKOR
2014
Kinetic Modeling of 11C-LY2795050, A Novel Antagonist Radiotracer for PET Imaging of the Kappa Opioid Receptor in Humans
Naganawa M, Zheng MQ, Nabulsi N, Tomasi G, Henry S, Lin SF, Ropchan J, Labaree D, Tauscher J, Neumeister A, Carson RE, Huang Y. Kinetic Modeling of 11C-LY2795050, A Novel Antagonist Radiotracer for PET Imaging of the Kappa Opioid Receptor in Humans. Cerebrovascular And Brain Metabolism Reviews 2014, 34: 1818-1825. PMID: 25182664, PMCID: PMC4269759, DOI: 10.1038/jcbfm.2014.150.Peer-Reviewed Original ResearchConceptsKappa-opioid receptorsMultilinear analysis 1Opioid receptorsNovel kappa opioid receptorDistribution volumePositron emission tomography (PET) imagingEmission Tomography ImagingLow intersubject variabilityTwo-tissue compartment modelAntagonist radiotracersOral naltrexoneNondisplaceable distribution volumeBaseline scanLY2795050Human studiesArterial input functionPET imagingTomography imagingIntersubject variabilityNaltrexoneEvaluation of the agonist PET radioligand [11C]GR103545 to image kappa opioid receptor in humans: Kinetic model selection, test–retest reproducibility and receptor occupancy by the antagonist PF-04455242
Naganawa M, Jacobsen LK, Zheng MQ, Lin SF, Banerjee A, Byon W, Weinzimmer D, Tomasi G, Nabulsi N, Grimwood S, Badura LL, Carson RE, McCarthy TJ, Huang Y. Evaluation of the agonist PET radioligand [11C]GR103545 to image kappa opioid receptor in humans: Kinetic model selection, test–retest reproducibility and receptor occupancy by the antagonist PF-04455242. NeuroImage 2014, 99: 69-79. PMID: 24844744, PMCID: PMC4140089, DOI: 10.1016/j.neuroimage.2014.05.033.Peer-Reviewed Original ResearchConceptsKappa-opioid receptorsTest-retest reproducibilityTest-retest variabilityAbsolute test-retest variabilityPF-04455242Time-activity curvesIntra-class coefficientOpioid receptorsRegional time-activity curvesMetabolite-corrected arterial input functionHuman positron emission tomography studiesPositron emission tomography studySelective KOR antagonistEmission tomography studiesReceptor occupancy studiesSuitable reference regionHalf maximal inhibitory concentrationAgonist tracersRegional VTAgonist PET radioligandOral doseKOR antagonistsMaximal inhibitory concentrationOral administrationPreclinical models
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
2012
Differential effects of age on human striatal adenosine A1 and A2A receptors
Mishina M, Kimura Y, Naganawa M, Ishii K, Oda K, Sakata M, Toyohara J, Kobayashi S, Katayama Y, Ishiwata K. Differential effects of age on human striatal adenosine A1 and A2A receptors. Synapse 2012, 66: 832-839. PMID: 22623181, DOI: 10.1002/syn.21573.Peer-Reviewed Original ResearchConceptsDistribution volume ratioEffect of ageCaudate nucleusPET scanningAge-related decreaseElderly subjectsElderly volunteersAdenosine A1Healthy subjectsPET scansA2A receptorsYoung subjectsHuman striatumStriatumReceptorsAgePutamenDifferential effectsPrevious reportsSubjectsAdenosineDistribution of adenosinePropylxanthineHead