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
A metabolically stable PET tracer for imaging synaptic vesicle protein 2A: synthesis and preclinical characterization of [18F]SDM-16
Zheng C, Holden D, Zheng MQ, Pracitto R, Wilcox KC, Lindemann M, Felchner Z, Zhang L, Tong J, Fowles K, Finnema SJ, Nabulsi N, Carson RE, Huang Y, Cai Z. A metabolically stable PET tracer for imaging synaptic vesicle protein 2A: synthesis and preclinical characterization of [18F]SDM-16. European Journal Of Nuclear Medicine And Molecular Imaging 2021, 49: 1482-1496. PMID: 34761284, PMCID: PMC8940841, DOI: 10.1007/s00259-021-05597-5.Peer-Reviewed Original ResearchConceptsTest-retest variabilityVolume of distributionCentral nervous systemTime-activity curvesPET tracersCentrum semiovaleSynaptic vesicle protein 2AAbsolute test-retest variabilityWhole central nervous systemNonhuman primate brainPlasma free fractionBrain PET scansHigh specific bindingSpecific bindingNondisplaceable volumePlasma input functionNHP brainOne-tissue compartment modelArterial bloodRegional time-activity curvesPET scansNervous systemPrimate brainMonkey brainPreclinical characterizationImaging 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 disordersAssessment of test-retest reproducibility of [18F]SynVesT-1, a novel radiotracer for PET imaging of synaptic vesicle glycoprotein 2A
Li S, Naganawa M, Pracitto R, Najafzadeh S, Holden D, Henry S, Matuskey D, Emery PR, Cai Z, Ropchan J, Nabulsi N, Carson RE, Huang Y. Assessment of test-retest reproducibility of [18F]SynVesT-1, a novel radiotracer for PET imaging of synaptic vesicle glycoprotein 2A. European Journal Of Nuclear Medicine And Molecular Imaging 2021, 48: 1327-1338. PMID: 33416954, DOI: 10.1007/s00259-020-05149-3.Peer-Reviewed Original ResearchConceptsTest-retest reproducibilityTime-activity curvesBPND valuesNonhuman primatesAbsolute test-retest variabilitySynaptic vesicle glycoprotein 2AHigh brain uptakeNon-displaceable binding potentialExcellent test-retest reproducibilityGray matter areasHealthy human subjectsHigh uptakeTest-retest variabilityDynamic PET scanningTest-retest reliabilityBrain uptakeDistribution volume valuesCentrum semiovaleUrinary bladderOne-tissue compartment modelMaximum SUVPET scanningPET scansTracer uptakeBrain disorders
2020
First-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 regionRadioligandHuman adult and adolescent biodistribution and dosimetry of the synaptic vesicle glycoprotein 2A radioligand 11C-UCB-J
Bini J, Holden D, Fontaine K, Mulnix T, Lu Y, Matuskey D, Ropchan J, Nabulsi N, Huang Y, Carson RE. Human adult and adolescent biodistribution and dosimetry of the synaptic vesicle glycoprotein 2A radioligand 11C-UCB-J. EJNMMI Research 2020, 10: 83. PMID: 32666239, PMCID: PMC7359974, DOI: 10.1186/s13550-020-00670-w.Peer-Reviewed Original ResearchDose-limiting organUrinary bladderTime-activity curvesSynaptic densityOLINDA/EXM 1.0 softwareWhole-body PET scansWhole-body scanHuman adultsDose limitTotal radiation doseGastrointestinal tractPET scansHealthy adultsInjected activityRegion of interestLarge intestineNeuropsychiatric disordersEffective doseRelevant disordersBladderLiverRadiation doseAdultsMBqHigh uptakeKinetic 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 ResearchConceptsTest-retest reproducibilityΚ-opioid receptorsRegional time-activity curvesTest-retest variabilityTime-activity curves
2019
In vivo 5-HT6 and 5-HT2A receptor availability in antipsychotic treated schizophrenia patients vs. unmedicated healthy humans measured with [11C]GSK215083 PET
Radhakrishnan R, Matuskey D, Nabulsi N, Gaiser E, Gallezot JD, Henry S, Planeta B, Lin SF, Ropchan J, Huang Y, Carson RE, D'Souza DC. In vivo 5-HT6 and 5-HT2A receptor availability in antipsychotic treated schizophrenia patients vs. unmedicated healthy humans measured with [11C]GSK215083 PET. Psychiatry Research Neuroimaging 2019, 295: 111007. PMID: 31760336, DOI: 10.1016/j.pscychresns.2019.111007.Peer-Reviewed Original ResearchConceptsHealthy male controlsPositron emission tomographyMultilinear analysis 1Antipsychotic treatmentLower BPFrontal cortexReceptor availabilityAge-matched healthy male controlsDifferent second-generation antipsychoticsSteady-state troughPeak serum levelsSecond-generation antipsychoticsPotential therapeutic targetMale patientsSerum levelsHealthy humansTherapeutic targetSchizophrenia patientsTime-activity curvesMale controlsCognitive impairmentEmission tomographyVentral striatumPatientsSchizophreniaSynthesis and in vivo evaluation of [18F]UCB-J for PET imaging of synaptic vesicle glycoprotein 2A (SV2A)
Li S, Cai Z, Zhang W, Holden D, Lin SF, Finnema SJ, Shirali A, Ropchan J, Carre S, Mercier J, Carson RE, Nabulsi N, Huang Y. Synthesis and in vivo evaluation of [18F]UCB-J for PET imaging of synaptic vesicle glycoprotein 2A (SV2A). European Journal Of Nuclear Medicine And Molecular Imaging 2019, 46: 1952-1965. PMID: 31175396, PMCID: PMC6810698, DOI: 10.1007/s00259-019-04357-w.Peer-Reviewed Original ResearchConceptsSynaptic vesicle glycoprotein 2AHigh specific binding signalsNonhuman primatesPET imagingHigh brain uptakeRegional distribution volumesBrain uptakeSynaptic densityOne-tissue compartment modelExcellent imaging agentRegional time-activity curvesVivo biomarkersArterial samplesSpecific binding signalsPsychiatric diseasesTime-activity curvesAlzheimer's diseaseDistribution volumeNeuropsychiatric disordersRadioactive metabolitesRhesus monkeysPET radiotracersVivo evaluationDiseaseImaging agentSocial 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 volumesImaging the Enzyme 11β-Hydroxysteroid Dehydrogenase Type 1 with PET: Evaluation of the Novel Radiotracer 11C-AS2471907 in Human Brain
Gallezot JD, Nabulsi N, Henry S, Pracitto R, Planeta B, Ropchan J, Lin SF, Labaree D, Kapinos M, Shirali A, Lara-Jaime T, Gao H, Matuskey D, Walzer M, Marek GJ, Bellaire S, Yuan N, Carson RE, Huang Y. Imaging the Enzyme 11β-Hydroxysteroid Dehydrogenase Type 1 with PET: Evaluation of the Novel Radiotracer 11C-AS2471907 in Human Brain. Journal Of Nuclear Medicine 2019, 60: 1140-1146. PMID: 30877174, DOI: 10.2967/jnumed.118.219766.Peer-Reviewed Original ResearchConceptsTest-retest variabilityNondisplaceable distribution volumeOccipital cortexEnzyme 11β-hydroxysteroid dehydrogenase type 1White matterDistribution volumeTreatment of depressionDehydrogenase type 1Large cortical regionsPosttraumatic stress disorderHuman brainAdditional scansIntraclass correlation coefficientAge-related cognitive functionBolus administrationFrontal cortexCaudate nucleusAdipose tissueTime-activity curvesNovel radiotracersGlucocorticoid levelsParietal cortexCortical regionsPattern of uptakeType 1Evaluation of 11C-LSN3172176 as a Novel PET Tracer for Imaging M1 Muscarinic Acetylcholine Receptors in Nonhuman Primates
Nabulsi NB, Holden D, Zheng MQ, Bois F, Lin SF, Najafzadeh S, Gao H, Ropchan J, Lara-Jaime T, Labaree D, Shirali A, Slieker L, Jesudason C, Barth V, Navarro A, Kant N, Carson RE, Huang Y. Evaluation of 11C-LSN3172176 as a Novel PET Tracer for Imaging M1 Muscarinic Acetylcholine Receptors in Nonhuman Primates. Journal Of Nuclear Medicine 2019, 60: 1147-1153. PMID: 30733324, DOI: 10.2967/jnumed.118.222034.Peer-Reviewed Original ResearchConceptsMuscarinic acetylcholine receptorsAcetylcholine receptorsNonhuman primatesM1 muscarinic acetylcholine receptorBrain time-activity curvesRich brain regionsArterial blood samplingNovel PET tracersSuitable reference regionRegional distribution volumesReference regionDevelopment of drugsBrain uptakeGlobus pallidusDistribution volume valuesNucleus accumbensBlood samplingPET scansTime-activity curvesCognitive impairmentAlzheimer's diseaseBrain regionsDistribution volumeSelective radiotracerRhesus monkeys
2018
2181 Age-related change in 5-HT6 receptor availability in healthy male volunteers measured with 11C-GSK215083 PET
Radhakrishnan R, Nabulsi N, Gaiser E, Gallezot J, Henry S, Planeta B, Lin S, Ropchan J, Williams W, Morris E, D’Souza D, Huang Y, Carson R, Matuskey D. 2181 Age-related change in 5-HT6 receptor availability in healthy male volunteers measured with 11C-GSK215083 PET. Journal Of Clinical And Translational Science 2018, 2: 3-4. PMCID: PMC6799074, DOI: 10.1017/cts.2018.44.Peer-Reviewed Original ResearchReceptor availabilityEffect of ageHealthy male volunteersSerotonin receptor 6Healthy male subjectsPotential therapeutic targetSignificant age-related declineMultilinear analysis-1 (MA1) methodAge-related changesAge-related declineMale volunteersTherapeutic targetNegative correlationTime-activity curvesReceptor 6PET ligandMale subjectsBrain regionsCortical regionsVentral striatumAgePutamenStriatumCaudateReference region
2017
A multi species evaluation of the radiation dosimetry of [11C]erlotinib, the radiolabeled analog of a clinically utilized tyrosine kinase inhibitor
Petrulli JR, Hansen SB, Abourbeh G, Yaqub M, Bahce I, Holden D, Huang Y, Nabulsi NB, Contessa JN, Mishani E, Lammertsma AA, Morris ED. A multi species evaluation of the radiation dosimetry of [11C]erlotinib, the radiolabeled analog of a clinically utilized tyrosine kinase inhibitor. Nuclear Medicine And Biology 2017, 47: 56-61. PMID: 28126682, PMCID: PMC5360653, DOI: 10.1016/j.nucmedbio.2016.12.009.Peer-Reviewed Original ResearchConceptsTyrosine kinase inhibitorsTime-activity curvesEquivalent doseNon-small cell lung cancer patientsStage IIIA NSCLC patientsEpidermal growth factor receptor (EGFR) mutationsCell lung cancer patientsCritical organsKinase inhibitorsIIIA NSCLC patientsLung cancer patientsHighest equivalent doseTime-integrated activity coefficientsWhole bodyMean equivalent dosesRhesus macaque monkeysNSCLC patientsDosimetry profileCancer patientsGallbladder wallReceptor mutationsMacaque monkeysIdentifiable organsInjected activityEffective dose
2016
First-in-Human Assessment of the Novel PDE2A PET Radiotracer 18F-PF-05270430
Naganawa M, Waterhouse RN, Nabulsi N, Lin SF, Labaree D, Ropchan J, Tarabar S, DeMartinis N, Ogden A, Banerjee A, Huang Y, Carson RE. First-in-Human Assessment of the Novel PDE2A PET Radiotracer 18F-PF-05270430. Journal Of Nuclear Medicine 2016, 57: 1388-1395. PMID: 27103022, PMCID: PMC5093918, DOI: 10.2967/jnumed.115.166850.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAzabicyclo CompoundsAzetidinesBrainComputer SimulationCyclic Nucleotide Phosphodiesterases, Type 2Feasibility StudiesFemaleHumansIsotope LabelingMacaca mulattaMaleMetabolic Clearance RateModels, BiologicalMolecular ImagingOrgan SpecificityPilot ProjectsPositron-Emission TomographyRadiopharmaceuticalsReproducibility of ResultsSensitivity and SpecificityTissue DistributionConceptsTest-retest variabilityHuman studiesPET ligandWhite matterNeocortical regionsMultilinear analysis 1MSv/MBqHealthy male subjectsDetectable pharmacologic effectsAppropriate tracer kinetic modelsTest-retest protocolAdverse eventsBrain uptakePharmacologic effectsRegional time-activity curvesTarget doseTime-activity curvesTracer uptakeMale subjectsWhole brainBrain regionsEffective doseCritical organsPET radiotracersNonhuman primates
2014
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
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