2022
Neurotransmitter transporter occupancy following administration of centanafadine sustained-release tablets: A phase 1 study in healthy male adults
Matuskey D, Gallezot J, Nabulsi N, Henry S, Torres K, Dias M, Angarita G, Huang Y, Shoaf S, Carson R, Mehrotra S. Neurotransmitter transporter occupancy following administration of centanafadine sustained-release tablets: A phase 1 study in healthy male adults. Journal Of Psychopharmacology 2022, 37: 164-171. PMID: 36515395, PMCID: PMC9912308, DOI: 10.1177/02698811221140008.Peer-Reviewed Original ResearchAge, gender and body-mass-index relationships with in vivo CB1 receptor availability in healthy humans measured with [11C]OMAR PET
Radhakrishnan R, Worhunsky PD, Zheng MQ, Najafzadeh S, Gallezot JD, Planeta B, Henry S, Nabulsi N, Ranganathan M, Skosnik PD, Pittman B, Cyril D'Souza D, Carson RE, Huang Y, Potenza MN, Matuskey D. Age, gender and body-mass-index relationships with in vivo CB1 receptor availability in healthy humans measured with [11C]OMAR PET. NeuroImage 2022, 264: 119674. PMID: 36243269, DOI: 10.1016/j.neuroimage.2022.119674.Peer-Reviewed Original Research
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 regionRadioligandKinetic 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
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 striatumPatientsSchizophreniaSocial 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 dosesBrivaracetamImaging 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 1
2018
Age-Related Change in 5-HT6 Receptor Availability in Healthy Male Volunteers Measured with 11C-GSK215083 PET
Radhakrishnan R, Nabulsi N, Gaiser E, Gallezot JD, Henry S, Planeta B, Lin SF, Ropchan J, Williams W, Morris E, D'Souza DC, Huang Y, Carson RE, Matuskey D. Age-Related Change in 5-HT6 Receptor Availability in Healthy Male Volunteers Measured with 11C-GSK215083 PET. Journal Of Nuclear Medicine 2018, 59: 1445-1450. PMID: 29626125, PMCID: PMC6126437, DOI: 10.2967/jnumed.117.206516.Peer-Reviewed Original Research
2015
Preclinical to Clinical Translation of CNS Transporter Occupancy of TD-9855, a Novel Norepinephrine and Serotonin Reuptake Inhibitor
Smith J, Patil D, Daniels O, Ding YS, Gallezot JD, Henry S, Kim K, Kshirsagar S, Martin W, Obedencio G, Stangeland E, Tsuruda P, Williams W, Carson R, Patil. Preclinical to Clinical Translation of CNS Transporter Occupancy of TD-9855, a Novel Norepinephrine and Serotonin Reuptake Inhibitor. The International Journal Of Neuropsychopharmacology 2015, 18: pyu027. PMID: 25522383, PMCID: PMC4368888, DOI: 10.1093/ijnp/pyu027.Peer-Reviewed Original ResearchMeSH KeywordsAdultAniline CompoundsAnimalsBlood Chemical AnalysisBrainHalf-LifeHumansMagnetic Resonance ImagingMaleModels, BiologicalMorpholinesNeurotransmitter Uptake InhibitorsNorepinephrine Plasma Membrane Transport ProteinsPhenyl EthersPiperidinesPositron-Emission TomographyRadiopharmaceuticalsRats, Sprague-DawleyReboxetineSerotonin Plasma Membrane Transport ProteinsSpinal CordSulfidesConceptsReuptake inhibitorsPositron emission tomographyNorepinephrine transporterSerotonin transporterSerotonin reuptake inhibitorsSingle oral doseUnique clinical profileMonoamine reuptake inhibitorsFuture clinical evaluationRat spinal cordNET occupancySERT occupancyClinical profileOral dosePlasma levelsTransporter profilesClinical evaluationSpinal cordTransporter occupancyCNS penetrationHealthy malesPharmacodynamic modelingNorepinephrineEmission tomographyPET studies
2012
Age Effects on Serotonin Receptor 1B as Assessed by PET
Matuskey D, Pittman B, Planeta-Wilson B, Walderhaug E, Henry S, Gallezot JD, Nabulsi N, Ding YS, Bhagwagar Z, Malison R, Carson RE, Neumeister A. Age Effects on Serotonin Receptor 1B as Assessed by PET. Journal Of Nuclear Medicine 2012, 53: 1411-1414. PMID: 22851636, PMCID: PMC3690814, DOI: 10.2967/jnumed.112.103598.Peer-Reviewed Original ResearchConceptsMultilinear reference tissue modelGray matter atrophyReceptor 1BAge-related gray matter atrophyIndividual cortical regionsSerotonin receptor 1BPrevious imaging studiesSerotonin measuresReference tissue modelAge-related declineMatter atrophyHealthy subjectsHealthy adultsGray matterImaging studiesCortical regionsPET imagingSubject underwentMultiple comparisonsCortexNegative associationAge effectsAgeAtrophyPutamenNormative database of the serotonergic system in healthy subjects using multi-tracer PET
Savli M, Bauer A, Mitterhauser M, Ding Y, Hahn A, Kroll T, Neumeister A, Haeusler D, Ungersboeck J, Henry S, Isfahani S, Rattay F, Wadsak W, Kasper S, Lanzenberger R. Normative database of the serotonergic system in healthy subjects using multi-tracer PET. NeuroImage 2012, 63: 447-459. PMID: 22789740, DOI: 10.1016/j.neuroimage.2012.07.001.Peer-Reviewed Original ResearchConceptsReceptor subtypesSerotonergic systemPmol/Healthy subjectsNeuropsychiatric disordersPostsynaptic receptor subtypesDifferent receptor subtypesHealthy human subjectsPost-traumatic stress disorderAttention-deficit/hyperactivity disorderDeficit/hyperactivity disorderExcitatory receptorsObsessive-compulsive disorderPost-mortem dataSleep disturbancesBP valuesMost neuropsychiatric disordersPET scansMajor inhibitorySelective radioligandSuicidal behaviorPET studiesStress disorderBrodmann areasAnxiety disorders