Featured Publications
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 zone
2023
Relationships of in vivo brain norepinephrine transporter and age, BMI, and gender
Koohsari S, Sadabad F, Pittman B, Gallezot J, Carson R, van Dyck C, Li C, Potenza M, Matuskey D. Relationships of in vivo brain norepinephrine transporter and age, BMI, and gender. Synapse 2023, 77: e22279. PMID: 37382240, PMCID: PMC10416616, DOI: 10.1002/syn.22279.Peer-Reviewed Original ResearchConceptsBody mass indexMultilinear reference tissue model 2Gender-related differencesBrain norepinephrine transportersNorepinephrine transporterAge-related declineStructural MR scansBrain regionsReference tissue model 2Mass indexRaphe nucleusLocus coeruleusOccipital cortexBMI relationshipHealthy adultsHigh-resolution research tomographAvailable radiotracersHealthy participantsMR scansAgeAnatomic templateReference regionNegative associationNet availabilityPotential age
2021
Identifying brain networks in synaptic density PET (11C-UCB-J) with independent component analysis
Fang XT, Toyonaga T, Hillmer AT, Matuskey D, Holmes SE, Radhakrishnan R, Mecca AP, van Dyck CH, D’Souza D, Esterlis I, Worhunsky PD, Carson RE. Identifying brain networks in synaptic density PET (11C-UCB-J) with independent component analysis. NeuroImage 2021, 237: 118167. PMID: 34000404, PMCID: PMC8452380, DOI: 10.1016/j.neuroimage.2021.118167.Peer-Reviewed Original ResearchConceptsSynaptic densityResting-state functional magnetic resonance imagingSynaptic vesicle protein 2ALevel-dependent signal fluctuationsBrain networksFunctional magnetic resonance imagingMagnetic resonance imagingAge-related changesHealthy controlsResonance imagingRs-fMRIEffects of sexProtein 2AMultiple comparisonsHuman brainAgePotential utilitySexFirst evidenceCovariance patternsPET 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
PTSD is associated with neuroimmune suppression: evidence from PET imaging and postmortem transcriptomic studies
Bhatt S, Hillmer AT, Girgenti MJ, Rusowicz A, Kapinos M, Nabulsi N, Huang Y, Matuskey D, Angarita GA, Esterlis I, Davis MT, Southwick SM, Friedman MJ, Duman R, Carson R, Krystal J, Pietrzak R, Cosgrove K. PTSD is associated with neuroimmune suppression: evidence from PET imaging and postmortem transcriptomic studies. Nature Communications 2020, 11: 2360. PMID: 32398677, PMCID: PMC7217830, DOI: 10.1038/s41467-020-15930-5.Peer-Reviewed Original ResearchMeSH KeywordsAcetamidesAdaptor Proteins, Signal TransducingAdultBrainCase-Control StudiesFemaleGene Expression ProfilingHealthy VolunteersHumansMaleMicrogliaMiddle AgedPositron-Emission TomographyPyridinesRadiopharmaceuticalsReceptors, GABAReceptors, Tumor Necrosis Factor, Member 14Sex FactorsStress Disorders, Post-TraumaticYoung AdultConceptsPosttraumatic stress disorderPeripheral immune activationImmune activationHigher C-reactive protein levelsC-reactive protein levelsTSPO availabilityTranslocator proteinBrain microglial activationTomography brain imagingStress-related pathophysiologyPositron emission tomography (PET) brain imagingNeuroimmune activationMicroglial activationPTSD symptom severityImmunologic regulationPostmortem studiesPTSD subgroupHealthy individualsSymptom severityTrauma exposurePTSD groupStress disorderLower relative expressionBrain imagingPET imagingKinetic 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
Measuring the effects of ketamine on mGluR5 using [18F]FPEB and PET
Holmes SE, Gallezot JD, Davis MT, DellaGioia N, Matuskey D, Nabulsi N, Krystal JH, Javitch JA, DeLorenzo C, Carson RE, Esterlis I. Measuring the effects of ketamine on mGluR5 using [18F]FPEB and PET. Cerebrovascular And Brain Metabolism Reviews 2019, 40: 2254-2264. PMID: 31744389, PMCID: PMC7585925, DOI: 10.1177/0271678x19886316.Peer-Reviewed Original ResearchConceptsEffects of ketamineKetamine infusionGlutamate transmissionMetabotropic glutamate receptor 5Ketamine-induced effectsKetamine-induced changesGlutamate receptor 5Promising treatment targetDrug challenge studiesTwo-tissue compartment modelMGluR5 radioligandBlood pressureMGluR5 availabilityBaseline scanOutcome measuresHealthy subjectsHeart ratePsychiatric disordersReceptor 5Modulatory effectsMGluR5Treatment targetsChallenge studiesArterial input functionChallenge paradigmNorepinephrine transporter availability in brown fat is reduced in obesity: a human PET study with [11C] MRB
Sanchez-Rangel E, Gallezot JD, Yeckel CW, Lam W, Belfort-DeAguiar R, Chen MK, Carson RE, Sherwin R, Hwang JJ. Norepinephrine transporter availability in brown fat is reduced in obesity: a human PET study with [11C] MRB. International Journal Of Obesity 2019, 44: 964-967. PMID: 31636373, PMCID: PMC7259982, DOI: 10.1038/s41366-019-0471-4.Peer-Reviewed Original ResearchConceptsBrown adipose tissueDetectable brown adipose tissueDistribution volume ratioMultilinear reference tissue model 2Norepinephrine transporterSympathetic innervationNorepinephrine transporter availabilityHuman brown adipose tissueDense sympathetic innervationPET-CT imagingReference tissue model 2Human PET studiesSupraclavicular regionCaucasian womenTransporter availabilityOccipital cortexObesityTherapeutic targetAdipose tissueBrown fatPET studiesWomenInnervationSelective ligandsEnergy-dissipating propertiesPET 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 antibodiesEffects of age, BMI and sex on the glial cell marker TSPO — a multicentre [11C]PBR28 HRRT PET study
Tuisku J, Plavén-Sigray P, Gaiser EC, Airas L, Al-Abdulrasul H, Brück A, Carson RE, Chen MK, Cosgrove KP, Ekblad L, Esterlis I, Farde L, Forsberg A, Halldin C, Helin S, Kosek E, Lekander M, Lindgren N, Marjamäki P, Rissanen E, Sucksdorff M, Varrone A, Collste K, Gallezot J, Hillmer A, Huang Y, Höglund C, Johansson J, Jucaite A, Lampa J, Nabulsi N, Pittman B, Sandiego C, Stenkrona P, Rinne J, Matuskey D, Cervenka S. Effects of age, BMI and sex on the glial cell marker TSPO — a multicentre [11C]PBR28 HRRT PET study. European Journal Of Nuclear Medicine And Molecular Imaging 2019, 46: 2329-2338. PMID: 31363804, PMCID: PMC6717599, DOI: 10.1007/s00259-019-04403-7.Peer-Reviewed Original ResearchConceptsBody mass indexPositron emission tomographyEffect of ageMultilinear analysis 1PET centersGlobal gray matterMass indexSubgroup analysisClinical studiesTSPO levelsHealthy subjectsTurku PET CentreHealthy volunteersPositive correlationTemporal cortexTSPO genotypeIndividual biological propertiesMale subjectsPurposeThe purposeConclusionThese findingsLinear mixed effects modelsGray matterParietal cortexSignificant negative correlationEmission tomography
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 engagementPotentiationSchizophrenia
2016
Determination of receptor occupancy in the presence of mass dose: [11C]GSK189254 PET imaging of histamine H3 receptor occupancy by PF-03654746
Gallezot JD, Planeta B, Nabulsi N, Palumbo D, Li X, Liu J, Rowinski C, Chidsey K, Labaree D, Ropchan J, Lin SF, Sawant-Basak A, McCarthy TJ, Schmidt AW, Huang Y, Carson RE. Determination of receptor occupancy in the presence of mass dose: [11C]GSK189254 PET imaging of histamine H3 receptor occupancy by PF-03654746. Cerebrovascular And Brain Metabolism Reviews 2016, 37: 1095-1107. PMID: 27207170, PMCID: PMC5363483, DOI: 10.1177/0271678x16650697.Peer-Reviewed Original ResearchImaging of cerebral α4β2* nicotinic acetylcholine receptors with (−)-[18F]Flubatine PET: Implementation of bolus plus constant infusion and sensitivity to acetylcholine in human brain
Hillmer AT, Esterlis I, Gallezot JD, Bois F, Zheng MQ, Nabulsi N, Lin SF, Papke RL, Huang Y, Sabri O, Carson RE, Cosgrove KP. Imaging of cerebral α4β2* nicotinic acetylcholine receptors with (−)-[18F]Flubatine PET: Implementation of bolus plus constant infusion and sensitivity to acetylcholine in human brain. NeuroImage 2016, 141: 71-80. PMID: 27426839, PMCID: PMC5026941, DOI: 10.1016/j.neuroimage.2016.07.026.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAdultBenzamidesBrainBridged Bicyclo Compounds, HeterocyclicComputer SimulationHumansImage Interpretation, Computer-AssistedInfusions, IntraventricularMetabolic Clearance RateMiddle AgedModels, NeurologicalMolecular ImagingNeurotransmitter AgentsPositron-Emission TomographyRadiopharmaceuticalsReceptors, NicotinicReproducibility of ResultsSensitivity and SpecificityTissue DistributionYoung AdultConceptsGray matter regions
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 volumeImaging robust microglial activation after lipopolysaccharide administration in humans with PET
Sandiego CM, Gallezot JD, Pittman B, Nabulsi N, Lim K, Lin SF, Matuskey D, Lee JY, O’Connor K, Huang Y, Carson RE, Hannestad J, Cosgrove KP. Imaging robust microglial activation after lipopolysaccharide administration in humans with PET. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 12468-12473. PMID: 26385967, PMCID: PMC4603509, DOI: 10.1073/pnas.1511003112.Peer-Reviewed Original ResearchConceptsMicroglial activationBrain microglial activationLPS administrationInflammatory cytokinesLPS challengeRobust microglial activationSystemic LPS challengeActivation of microgliaInnate immune cellsVital sign changesHealthy male subjectsEscherichia coli lipopolysaccharidePositron emission tomography (PET) radiotracerNeuroinflammatory responseSystemic inflammationLipopolysaccharide administrationAntiinflammatory effectsBlood levelsImmune cellsNew medicationsSystemic administrationColi lipopolysaccharidePET scansPsychiatric diseasesMale subjectsReduced Brain Cannabinoid Receptor Availability in Schizophrenia
Ranganathan M, Cortes-Briones J, Radhakrishnan R, Thurnauer H, Planeta B, Skosnik P, Gao H, Labaree D, Neumeister A, Pittman B, Surti T, Huang Y, Carson RE, D’Souza D. Reduced Brain Cannabinoid Receptor Availability in Schizophrenia. Biological Psychiatry 2015, 79: 997-1005. PMID: 26432420, PMCID: PMC4884543, DOI: 10.1016/j.biopsych.2015.08.021.Peer-Reviewed Original ResearchConceptsHealthy control subjectsSCZ subjectsCB1R availabilityECB systemMale healthy control subjectsBody mass indexAge-matched male healthy control subjectsPathophysiology of schizophreniaPositron emission tomographyPosterior cingulate cortexPresence of abnormalitiesMass indexControl subjectsEndocannabinoid systemTobacco useReceptor availabilityCingulate cortexEmission tomography dataBrain regionsEmission tomographySelective radiotracerVivo measuresRegional volumesSchizophreniaPositron emission tomography dataTest–retest reproducibility of the metabotropic glutamate receptor 5 ligand [18F]FPEB with bolus plus constant infusion in humans
Park E, Sullivan JM, Planeta B, Gallezot JD, Lim K, Lin SF, Ropchan J, McCarthy TJ, Ding YS, Morris ED, Williams WA, Huang Y, Carson RE. Test–retest reproducibility of the metabotropic glutamate receptor 5 ligand [18F]FPEB with bolus plus constant infusion in humans. European Journal Of Nuclear Medicine And Molecular Imaging 2015, 42: 1530-1541. PMID: 26044120, PMCID: PMC5467218, DOI: 10.1007/s00259-015-3094-6.Peer-Reviewed Original ResearchConceptsVolume of distributionAbsolute test-retest variabilityCerebellar white matterTest-retest reproducibilityMetabotropic glutamate receptor 5Venous blood measurementsGlutamate receptor 5Healthy male subjectsPromising PET radioligandArterial blood concentrationPET imaging tracerTest-retest variabilityTwo-tissue compartment modelRegional BPNDVenous bloodBlood concentrationsArterial bloodReceptor 5Constant infusionMale subjectsWhite matterBlood measurementsGray matterNeuropsychiatric diseasesPET radioligandImaging human brown adipose tissue under room temperature conditions with 11C-MRB, a selective norepinephrine transporter PET ligand
Hwang JJ, Yeckel CW, Gallezot JD, Aguiar RB, Ersahin D, Gao H, Kapinos M, Nabulsi N, Huang Y, Cheng D, Carson RE, Sherwin R, Ding YS. Imaging human brown adipose tissue under room temperature conditions with 11C-MRB, a selective norepinephrine transporter PET ligand. Metabolism 2015, 64: 747-755. PMID: 25798999, PMCID: PMC4408242, DOI: 10.1016/j.metabol.2015.03.001.Peer-Reviewed Original ResearchConceptsBrown adipose tissueDistribution volume ratioSympathetic nervous systemAdipose tissueRole of BATCold stimulationFDG PET-CT imagingNorepinephrine transporterSupraclavicular brown adipose tissueHuman brown adipose tissueTotal body fatLean body massCold-stimulated conditionsBody temperaturePET-CT imagingBioelectrical impedance analysisCore body temperatureFDG uptakePET-CTOccipital cortexBody fatNervous systemBody compositionPET ligandBasal stateTest–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