2022
Differences in Quantification of the Metabotropic Glutamate Receptor 5 Across Bipolar Disorder and Major Depressive Disorder
Holmes S, Asch R, Davis M, DellaGioia N, Pashankar N, Gallezot J, Nabulsi N, Matuskey D, Sanacora G, Carson R, Blumberg H, Esterlis I. Differences in Quantification of the Metabotropic Glutamate Receptor 5 Across Bipolar Disorder and Major Depressive Disorder. Biological Psychiatry 2022, 93: 1099-1107. PMID: 36764853, PMCID: PMC10164841, DOI: 10.1016/j.biopsych.2022.10.018.Peer-Reviewed Original ResearchMeSH KeywordsBipolar DisorderDepressive Disorder, MajorHumansMagnetic Resonance ImagingPositron-Emission TomographyPrefrontal CortexReceptor, Metabotropic Glutamate 5ConceptsMajor depressive disorderMetabotropic glutamate receptor 5Glutamate receptor 5MGluR5 availabilityBipolar disorderPositron emission tomographyHC groupDepressive disorderReceptor 5Emission tomographyHealthy control individualsPossible treatment targetsGlutamate transmissionBD depressionTreatment strategiesBD groupMGluR5Depressive symptomsNovel treatmentsCognitive alterationsTreatment targetsSynaptic plasticityControl individualsAccurate diagnosisSignificant negative correlationA 3D atlas of functional human brain energetic connectome based on neuropil distribution
Yu Y, Akif A, Herman P, Cao M, Rothman D, Carson R, Agarwal D, Evans A, Hyder F. A 3D atlas of functional human brain energetic connectome based on neuropil distribution. Cerebral Cortex 2022, 33: 3996-4012. PMID: 36104858, PMCID: PMC10068297, DOI: 10.1093/cercor/bhac322.Peer-Reviewed Original ResearchConceptsSynaptic densityCortical regionsHigher synapse densityHuman cortical circuitsFunctional imaging studiesCortical activity mapsVivo PET imagingNeuropil distributionGlucose oxidationSynapse densityCortical circuitsMetabolic rateSynaptic connectionsCortical energeticsImaging studiesHuman cortexPET imagingHistological stainingRecent evidenceCortexHuman brainBrainVoxel levelActivity ratesAtlas
2020
Binding of the synaptic vesicle radiotracer [11C]UCB-J is unchanged during functional brain activation using a visual stimulation task
Smart K, Liu H, Matuskey D, Chen MK, Torres K, Nabulsi N, Labaree D, Ropchan J, Hillmer AT, Huang Y, Carson RE. Binding of the synaptic vesicle radiotracer [11C]UCB-J is unchanged during functional brain activation using a visual stimulation task. Cerebrovascular And Brain Metabolism Reviews 2020, 41: 1067-1079. PMID: 32757741, PMCID: PMC8054713, DOI: 10.1177/0271678x20946198.Peer-Reviewed Original ResearchConceptsVisual cortexVisual stimulationPositron emission tomography radioligandBrain activationBlood flow increasesVolume of distributionPrimary visual cortexCheckerboard visual stimulationFunctional brain activationFunctional magnetic resonanceReference tissue modelFMRI BOLD responsesSynaptic densityVisual stimulation taskOne-tissue compartment modelHealthy volunteersNeuronal firingTomography radioligandPET scansTissue influxVivo measuresRobust increaseBOLD responseTracer influxStimulation task
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 paradigmA 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 dosesBrivaracetam
2018
Decreased VMAT2 in the pancreas of humans with type 2 diabetes mellitus measured in vivo by PET imaging
Cline GW, Naganawa M, Chen L, Chidsey K, Carvajal-Gonzalez S, Pawlak S, Rossulek M, Zhang Y, Bini J, McCarthy TJ, Carson RE, Calle RA. Decreased VMAT2 in the pancreas of humans with type 2 diabetes mellitus measured in vivo by PET imaging. Diabetologia 2018, 61: 2598-2607. PMID: 29721633, DOI: 10.1007/s00125-018-4624-0.Peer-Reviewed Original ResearchMeSH KeywordsDiabetes Mellitus, Type 2FemaleHumansInsulin-Secreting CellsMagnetic Resonance ImagingMaleMiddle AgedPancreasPositron-Emission TomographyVesicular Monoamine Transport ProteinsConceptsVesicular monoamine transporter type 2Type 2 diabetesBeta-cell massHealthy obese volunteersStandardised uptake value ratioBeta-cell functionTest-retest variabilityPancreas headTracer uptakeSUVR-1Type 2 diabetes mellitusType 2 diabetic participantsBeta-cell capacityConclusions/interpretationTheC-peptide AUCImpaired glucose toleranceType 2 diabetes pathophysiologyCell functionDeficient insulin secretionAcute insulin responsePancreas of humansUptake value ratioC-peptide releasePancreatic polypeptide cellsTransporter type 2Dose-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
2015
Measurement of Bmax and Kd with the Glycine Transporter 1 Radiotracer 18F-MK6577 using a Novel Multi-Infusion Paradigm
Xia Y, Zheng MQ, Holden D, Lin SF, Kapinos M, Ropchan J, Gallezot JD, Huang Y, Carson RE. Measurement of Bmax and Kd with the Glycine Transporter 1 Radiotracer 18F-MK6577 using a Novel Multi-Infusion Paradigm. Cerebrovascular And Brain Metabolism Reviews 2015, 35: 2001-2009. PMID: 26198176, PMCID: PMC4671121, DOI: 10.1038/jcbfm.2015.163.Peer-Reviewed Original ResearchConceptsGlycine transporter-1 inhibitorNew positron emission tomography radiotracerPositron emission tomography (PET) radiotracerPotential therapeutic agentNondisplaceable distribution volumeNMDA receptorsVivo affinityBaboon brainDistribution volumeBmax valuesTomography radiotracerTherapeutic agentsVivo KDBrainRank orderUnlabeled compoundsRadiotracerKdBrainstem11C-PBR28 imaging in multiple sclerosis patients and healthy controls: test-retest reproducibility and focal visualization of active white matter areas
Park E, Gallezot JD, Delgadillo A, Liu S, Planeta B, Lin SF, O’Connor K, Lim K, Lee JY, Chastre A, Chen MK, Seneca N, Leppert D, Huang Y, Carson RE, Pelletier D. 11C-PBR28 imaging in multiple sclerosis patients and healthy controls: test-retest reproducibility and focal visualization of active white matter areas. European Journal Of Nuclear Medicine And Molecular Imaging 2015, 42: 1081-1092. PMID: 25833352, DOI: 10.1007/s00259-015-3043-4.Peer-Reviewed Original ResearchConceptsNormal-appearing white matterVolume of distributionTest-retest variabilityWhole brain white matterHealthy controlsMicroglial activationTest-retest reproducibilityGray matterMultiple sclerosisMS subjectsWhite matterWhole brain gray matterGood test-retest reproducibilityAbsolute test-retest variabilityActive MS patientsPositron emission tomography (PET) ligandMultiple sclerosis patientsMain outcome measuresWhite matter areasMS WM lesionsBrain gray matterDemyelinating injuryTest-retest resultsVT valuesMS patientsPreclinical 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
Vascular burden and Alzheimer disease pathologic progression
Lo R, Jagust W, Weiner M, Aisen P, Weiner M, Aisen P, Petersen R, Jack C, Jagust W, Trojanowki J, Toga A, Beckett L, Green R, Saykin A, Morris J, Liu E, Green R, Montine T, Petersen R, Aisen P, Gamst A, Thomas R, Donohue M, Walter S, Gessert D, Sather T, Beckett L, Harvey D, Gamst A, Donohue M, Kornak J, Jack C, Dale A, Bernstein M, Felmlee J, Fox N, Thompson P, Schuff N, Alexander G, DeCarli C, Jagust W, Bandy D, Koeppe R, Foster N, Reiman E, Chen K, Mathis C, Morris J, Cairns N, Taylor-Reinwald L, Trojanowki J, Shaw L, Lee V, Korecka M, Toga A, Crawford K, Neu S, Saykin A, Foroud T, Potkin S, Shen L, Kachaturian Z, Frank R, Snyder P, Molchan S, Kaye J, Quinn J, Lind B, Dolen S, Schneider L, Pawluczyk S, Spann B, Brewer J, Vanderswag H, Heidebrink J, Lord J, Petersen R, Johnson K, Doody R, Villanueva-Meyer J, Chowdhury M, Stern Y, Honig L, Bell K, Morris J, Ances B, Carroll M, Leon S, Mintun M, Schneider S, Marson D, Griffith R, Clark D, Grossman H, Mitsis E, Romirowsky A, deToledo-Morrell L, Shah R, Duara R, Varon D, Roberts P, Albert M, Onyike C, Kielb S, Rusinek H, de Leon M, Glodzik L, De Santi S, Doraiswamy P, Petrella J, Coleman R, Arnold S, Karlawish J, Wolk D, Smith C, Jicha G, Hardy P, Lopez O, Oakley M, Simpson D, Porsteinsson A, Goldstein B, Martin K, Makino K, Ismail M, Brand C, Mulnard R, Thai G, Mc-Adams-Ortiz C, Womack K, Mathews D, Quiceno M, Diaz-Arrastia R, King R, Weiner M, Martin-Cook K, DeVous M, Levey A, Lah J, Cellar J, Burns J, Anderson H, Swerdlow R, Apostolova L, Lu P, Bartzokis G, Silverman D, Graff-Radford N, Parfitt F, Johnson H, Farlow M, Hake A, Matthews B, Herring S, van Dyck C, Carson R, MacAvoy M, Chertkow H, Bergman H, Hosein C, Black S, Stefanovic D, Caldwell C, Hsiung G, Feldman H, Mudge B, Assaly M, Kertesz A, Rogers J, Trost D, Bernick C, Munic D, Kerwin D, Mesulam M, Lipowski K, Wu C, Johnson N, Sadowsky C, Martinez W, Villena T, Turner R, Johnson K, Reynolds B, Sperling R, Johnson K, Marshall G, Frey M, Yesavage J, Taylor J, Lane B, Rosen A, Tinklenberg J, Sabbagh M, Belden C, Jacobson S, Kowall N, Killiany R, Budson A, Norbash A, Johnson P, Obisesan T, Wolday S, Bwayo S, Lerner A, Hudson L, Ogrocki P, Fletcher E, Carmichael O, Olichney J, DeCarli C, Kittur S, Borrie M, Lee T, Bartha D, Johnson S, Asthana S, Carlsson C, Potkin S, Preda A, Nguyen D, Tariot P, Fleisher A, Reeder S, Bates V, Capote H, Rainka M, Scharre D, Kataki M, Zimmerman E, Celmins D, Brown A, Pearlson G, Blank K, Anderson K, Saykin A, Santulli R, Schwartz E, Sink K, Williamson J, Garg P, Watkins F, Ott B, Querfurth H, Tremont G, Salloway S, Malloy P, Correia S, Rosen H, Miller B, Mintzer J, Longmire C, Spicer K, Finger E, Rachinsky I, Rogers J, Kertesz A, Drost D. Vascular burden and Alzheimer disease pathologic progression. Neurology 2012, 79: 1349-1355. PMID: 22972646, PMCID: PMC3448744, DOI: 10.1212/wnl.0b013e31826c1b9d.Peer-Reviewed Original ResearchConceptsWhite matter hyperintensitiesMild cognitive impairmentVascular burdenNormal cognitionPathologic progressionVascular contributionsDisease Neuroimaging InitiativeCognitive impairmentMRI biomarkersMRI white matter hyperintensitiesBaseline cardiovascular riskCardiovascular risk profileCardiovascular risk scoreLow FDG uptakeExecutive functionAlzheimer's disease biomarkersAlzheimer's Disease Neuroimaging InitiativeCardiovascular riskCerebrovascular riskPoorer executive functionHippocampal atrophyFDG uptakeSurrogate markerMatter hyperintensitiesRisk scoreIn Vivo Imaging of Endogenous Pancreatic β-Cell Mass in Healthy and Type 1 Diabetic Subjects Using 18F-Fluoropropyl-Dihydrotetrabenazine and PET
Normandin MD, Petersen KF, Ding YS, Lin SF, Naik S, Fowles K, Skovronsky DM, Herold KC, McCarthy TJ, Calle RA, Carson RE, Treadway JL, Cline GW. In Vivo Imaging of Endogenous Pancreatic β-Cell Mass in Healthy and Type 1 Diabetic Subjects Using 18F-Fluoropropyl-Dihydrotetrabenazine and PET. Journal Of Nuclear Medicine 2012, 53: 908-916. PMID: 22573821, PMCID: PMC3737743, DOI: 10.2967/jnumed.111.100545.Peer-Reviewed Original ResearchConceptsType 1 diabetes mellitusVesicular monoamine transporter type 2Pancreatic β-cell massStandardized uptake valueΒ-cell massDiabetes mellitusUptake valueType 1 diabetic subjectsΒ-cell densityHealthy control subjectsInsulin secretion capacityΒ-cell functionPathophysiology of diabetesTransporter type 2Nondisplaceable uptakeDiabetic subjectsControl subjectsDisease progressionClinical assessmentVMAT2 bindingRenal cortexTotal pancreasDTBZ PETEarly diagnosisInjected dose
2009
Kinetic Modeling of the Serotonin 5-HT1B Receptor Radioligand [11C]P943 in Humans
Gallezot JD, Nabulsi N, Neumeister A, Planeta-Wilson B, Williams WA, Singhal T, Kim S, Maguire RP, McCarthy T, Frost JJ, Huang Y, Ding YS, Carson RE. Kinetic Modeling of the Serotonin 5-HT1B Receptor Radioligand [11C]P943 in Humans. Cerebrovascular And Brain Metabolism Reviews 2009, 30: 196-210. PMID: 19773803, PMCID: PMC2949107, DOI: 10.1038/jcbfm.2009.195.Peer-Reviewed Original ResearchMeSH KeywordsBrainChromatography, High Pressure LiquidElectron Spin Resonance SpectroscopyHumansImage Processing, Computer-AssistedIsotope LabelingLinear ModelsMagnetic Resonance ImagingMental DisordersModels, StatisticalPiperazinesPositron-Emission TomographyPyrrolidinonesRadiopharmaceuticalsReceptor, Serotonin, 5-HT1B
1997
Regional cerebral blood flow throughout the sleep-wake cycle. An H2(15)O PET study.
Braun AR, Balkin TJ, Wesenten NJ, Carson RE, Varga M, Baldwin P, Selbie S, Belenky G, Herscovitch P. Regional cerebral blood flow throughout the sleep-wake cycle. An H2(15)O PET study. Brain 1997, 120: 1173-1197. PMID: 9236630, DOI: 10.1093/brain/120.7.1173.Peer-Reviewed Original ResearchConceptsSlow-wave sleepSleep-wake cycleHeteromodal association areasREM sleepBasal gangliaSensory cortexState-dependent changesAssociation cortexAssociation areasRegional cerebral blood flowRapid eye movement (REM) sleepActivity of limbicMesial temporal cortexCerebral blood flowEye movement sleepSecondary sensory cortexNormal male volunteersCharacteristics of sleepHeteromodal association cortexFrontoparietal association cortexUnimodal sensory areasREM sleep stateStages of sleepStatistical parametric mappingCentrencephalic structuresMultimodality Bayesian algorithm for image reconstruction in positron emission tomography: a tissue composition model
Sastry S, Carson RE. Multimodality Bayesian algorithm for image reconstruction in positron emission tomography: a tissue composition model. IEEE Transactions On Medical Imaging 1997, 16: 750-761. PMID: 9533576, DOI: 10.1109/42.650872.Peer-Reviewed Original Research