2024
First-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 imaging
2022
Drug characteristics derived from kinetic modeling: combined 11C-UCB-J human PET imaging with levetiracetam and brivaracetam occupancy of SV2A
Naganawa M, Gallezot J, Finnema S, Maguire R, Mercier J, Nabulsi N, Kervyn S, Henry S, Nicolas J, Huang Y, Chen M, Hannestad J, Klitgaard H, Stockis A, Carson R. Drug characteristics derived from kinetic modeling: combined 11C-UCB-J human PET imaging with levetiracetam and brivaracetam occupancy of SV2A. EJNMMI Research 2022, 12: 71. PMID: 36346513, PMCID: PMC9643320, DOI: 10.1186/s13550-022-00944-5.Peer-Reviewed Original ResearchTime-activity curvesBrain entryDrug concentrationsNon-human primate brainAnti-seizure activitySynaptic vesicle glycoprotein 2APlasma drug concentrationsPrevious human studiesBackgroundAntiepileptic drugsHealthy subjectsBlood samplesHuman studiesLevetiracetamPrimate brainEmission tomography dataBrivaracetamDistribution volumeArterial input functionBrainDrug characteristicsPositron emission tomography dataDrug entryFree fractionDrugsKinetic parameters k1
2021
Imaging Pituitary Vasopressin 1B Receptor in Humans with the PET Radiotracer 11C-TASP699
Naganawa M, Nabulsi NB, Matuskey D, Henry S, Ropchan J, Lin SF, Gao H, Pracitto R, Labaree D, Zhang MR, Suhara T, Nishino I, Sabia H, Ozaki S, Huang Y, Carson RE. Imaging Pituitary Vasopressin 1B Receptor in Humans with the PET Radiotracer 11C-TASP699. Journal Of Nuclear Medicine 2021, 63: 609-614. PMID: 34385336, DOI: 10.2967/jnumed.121.262430.Peer-Reviewed Original ResearchConceptsMultilinear analysis 1Test-retest variabilityPlasma concentrationsHealthy subjectsR occupancyR antagonistBrain regionsMetabolite-corrected arterial input functionAbsolute test-retest variabilityAdrenal axis activityNovel PET radiotracersSubstantial specific bindingDose-dependent fashionVasopressin 1b receptorTest-retest reproducibilityHalf maximal inhibitory concentrationAdverse eventsAxis activityOutcome measuresReceptor occupancyTime-activity curvesArginine vasopressinPosterior pituitaryDistribution volumeNeuropsychiatric disorders
2020
Assessment of population-based input functions for Patlak imaging of whole body dynamic 18F-FDG PET
Naganawa M, Gallezot JD, Shah V, Mulnix T, Young C, Dias M, Chen MK, Smith AM, Carson RE. Assessment of population-based input functions for Patlak imaging of whole body dynamic 18F-FDG PET. EJNMMI Physics 2020, 7: 67. PMID: 33226522, PMCID: PMC7683759, DOI: 10.1186/s40658-020-00330-x.Peer-Reviewed Original ResearchPopulation-based input functionImage-derived input functionInitial distribution volumeArterial input functionInjected doseBlood samplingWhole bodyStandard arterial input functionInitial plasma concentrationsArterial blood samplingOncological patientsPlasma concentrationsGold standard methodDistribution volumePET studiesPET imagingSubject heightInput functionAUCAUC valuesTest-retest dataClinical environmentLater time windowKi valuesImagingFirst-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 regionRadioligand
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 SUV
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 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
Test-retest variability of adenosine A2A binding in the human brain with 11C-TMSX and PET
Naganawa M, Mishina M, Sakata M, Oda K, Hiura M, Ishii K, Ishiwata K. Test-retest variability of adenosine A2A binding in the human brain with 11C-TMSX and PET. EJNMMI Research 2014, 4: 76. PMID: 25621197, PMCID: PMC4293456, DOI: 10.1186/s13550-014-0076-9.Peer-Reviewed Original ResearchTest-retest variabilityCerebral cortexCentrum semiovaleMethodsFive healthy volunteersNon-displaceable uptakeLow test-retest variabilityReference regionArterial blood samplingTest-retest reproducibilityCandidate reference regionsHuman brainTest-retest studyHealthy volunteersAdenosine A2ABlood samplingDistribution volumeInvasive methodNoninvasive methodReceptor quantificationBPNDCortexBrainPresent studySimilar levelsPETKinetic 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 variabilityNaltrexone
2013
Clinical doses of atomoxetine significantly occupy both norepinephrine and serotonin transports: Implications on treatment of depression and ADHD
Ding YS, Naganawa M, Gallezot JD, Nabulsi N, Lin SF, Ropchan J, Weinzimmer D, McCarthy TJ, Carson RE, Huang Y, Laruelle M. Clinical doses of atomoxetine significantly occupy both norepinephrine and serotonin transports: Implications on treatment of depression and ADHD. NeuroImage 2013, 86: 164-171. PMID: 23933039, DOI: 10.1016/j.neuroimage.2013.08.001.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic Uptake InhibitorsAnimalsAtomoxetine HydrochlorideAttention Deficit Disorder with HyperactivityBrainDepressionDose-Response Relationship, DrugMacaca mulattaNorepinephrine Plasma Membrane Transport ProteinsPositron-Emission TomographyPropylaminesSerotonin Plasma Membrane Transport ProteinsTissue DistributionConceptsTreatment of depressionNorepinephrine transporterComparative PET imaging studyMetabolite-corrected arterial input functionFinal infusion rateDoses of atomoxetineDose-dependent occupancyPET imaging studiesSelective serotonin transporter (SERT) ligandNon-human primatesPlasma levelsSelective blockadeSaline infusionClinical dosesTherapeutic effectInfusion rateRelevant dosePET scansAtomoxetineRelevant dosesSerotonin transporter ligandDistribution volumeImaging studiesRhesus monkeysArterial input function
2008
Shortened protocol in practical [11C]SA4503-PET studies for sigma1 receptor quantification
Sakata M, Kimura Y, Naganawa M, Ishikawa M, Oda K, Ishii K, Hashimoto K, Chihara K, Ishiwata K. Shortened protocol in practical [11C]SA4503-PET studies for sigma1 receptor quantification. Annals Of Nuclear Medicine 2008, 22: 143-146. PMID: 18311540, DOI: 10.1007/s12149-007-0088-x.Peer-Reviewed Original ResearchMeSH KeywordsAdultBrain ChemistryBrain MappingCarbon RadioisotopesClinical ProtocolsFluvoxamineHumansImage Interpretation, Computer-AssistedImage Processing, Computer-AssistedIsotope LabelingMaleParoxetinePiperazinesPositron-Emission TomographyRadioligand AssayRadiopharmaceuticalsReceptors, sigmaSelective Serotonin Reuptake InhibitorsTissue DistributionConceptsTotal distribution volumePET scansSelective serotonin reuptake inhibitorsSerotonin reuptake inhibitorsReuptake inhibitorsHealthy subjectsLogan plot analysisReceptor measurementsTomography diagnosisTime-activity curvesBrain disordersDistribution volumePET studiesReceptor quantificationTissue time-activity curvesScansCompartmental analysisFull-length protocolsPositron Emission Tomography DiagnosisPatientsPlot analysisRegion of interestProtocolDiagnosisAdministration
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 affinityImagingDVTDiseaseRadioligandBrainMapping 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
2005
Omission of serial arterial blood sampling in neuroreceptor imaging with independent component analysis
Naganawa M, Kimura Y, Nariai T, Ishii K, Oda K, Manabe Y, Chihara K, Ishiwata K. Omission of serial arterial blood sampling in neuroreceptor imaging with independent component analysis. NeuroImage 2005, 26: 885-890. PMID: 15955498, DOI: 10.1016/j.neuroimage.2005.02.025.Peer-Reviewed Original ResearchConceptsArterial blood samplingBlood samplingCerebral glucose metabolismAdenosine A1 receptorsTotal distribution volumeSerial arterial blood samplingLogan plotPET imagesPlasma time-activity curveA1 receptorsHealthy subjectsGlucose metabolismTime-activity curvesDistribution volumeBrain diseasesDVTReference regionSubjectsParametric imagesDynamic PET images