2020
Separating dopamine D2 and D3 receptor sources of [11C]-(+)-PHNO binding potential: Independent component analysis of competitive binding
Smart K, Gallezot JD, Nabulsi N, Labaree D, Zheng MQ, Huang Y, Carson RE, Hillmer AT, Worhunsky PD. Separating dopamine D2 and D3 receptor sources of [11C]-(+)-PHNO binding potential: Independent component analysis of competitive binding. NeuroImage 2020, 214: 116762. PMID: 32201327, PMCID: PMC7263955, DOI: 10.1016/j.neuroimage.2020.116762.Peer-Reviewed Original Research
2019
Kappa-opioid receptors, dynorphin, and cocaine addiction: a positron emission tomography study
Martinez D, Slifstein M, Matuskey D, Nabulsi N, Zheng MQ, Lin SF, Ropchan J, Urban N, Grassetti A, Chang D, Salling M, Foltin R, Carson RE, Huang Y. Kappa-opioid receptors, dynorphin, and cocaine addiction: a positron emission tomography study. Neuropsychopharmacology 2019, 44: 1720-1727. PMID: 31026862, PMCID: PMC6785004, DOI: 10.1038/s41386-019-0398-4.Peer-Reviewed Original ResearchConceptsCocaine use disorderStress-induced relapsePositron emission tomographyCocaine bingeKappa-opioid receptor/dynorphin systemKOR selective agonistPositron emission tomography studyKappa-opioid receptorsCold pressor testCocaine self-administration sessionsEmission tomography studiesSelf-administration sessionsStress-induced cocaineEndogenous dynorphinDynorphin systemHealthy controlsPressor testSelective agonistPET scansAnimal studiesKOR bindingReceptor availabilitySignificant associationBrain regionsEmission tomography
2016
Imaging 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 regionsComparative evaluation of two glycine transporter 1 radiotracers [11C]GSK931145 and [18F]MK‐6577 in baboons
Zheng MQ, Lin SF, Holden D, Naganawa M, Ropchan JR, Najafzaden S, Kapinos M, Tabriz M, Carson RE, Hamill TG, Huang Y. Comparative evaluation of two glycine transporter 1 radiotracers [11C]GSK931145 and [18F]MK‐6577 in baboons. Synapse 2016, 70: 112-120. PMID: 26671330, DOI: 10.1002/syn.21879.Peer-Reviewed Original ResearchAnimalsBenzamidesBrainBrain MappingCarbon RadioisotopesChromatography, High Pressure LiquidDrug Evaluation, PreclinicalFemaleGlycine AgentsGlycine Plasma Membrane Transport ProteinsKineticsLinear ModelsMagnetic Resonance ImagingMolecular StructurePapioPositron-Emission TomographyRadiopharmaceuticalsSulfonamides
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 volumePET imaging evaluation of [18F]DBT-10, a novel radioligand specific to α7 nicotinic acetylcholine receptors, in nonhuman primates
Hillmer AT, Zheng MQ, Li S, Scheunemann M, Lin SF, Holden D, Labaree D, Ropchan J, Teodoro R, Deuther-Conrad W, Carson RE, Brust P, Huang Y. PET imaging evaluation of [18F]DBT-10, a novel radioligand specific to α7 nicotinic acetylcholine receptors, in nonhuman primates. European Journal Of Nuclear Medicine And Molecular Imaging 2015, 43: 537-547. PMID: 26455500, PMCID: PMC4733418, DOI: 10.1007/s00259-015-3209-0.Peer-Reviewed Original ResearchConceptsPurposePositron emission tomographyDose-dependent blockadeStandardized uptake valueΑ7 nicotinic acetylcholine receptorNonhuman primatesPeak standardized uptake valueBaseline PET scanParent fractionEx vivo analysisPlasma free fractionNicotinic acetylcholine receptorsTotal distribution volumeBrain tissue samplesRegional rank orderTwo-tissue compartment modelSpecific radioligandFrontal cortexOccipital cortexNovel radioligandPET scansArterial plasmaAcetylcholine receptorsUptake valueAlzheimer's diseaseBrain tissueA Promising PET Tracer for Imaging of α7 Nicotinic Acetylcholine Receptors in the Brain: Design, Synthesis, and in Vivo Evaluation of a Dibenzothiophene-Based Radioligand
Teodoro R, Scheunemann M, Deuther-Conrad W, Wenzel B, Fasoli FM, Gotti C, Kranz M, Donat CK, Patt M, Hillmer A, Zheng MQ, Peters D, Steinbach J, Sabri O, Huang Y, Brust P. A Promising PET Tracer for Imaging of α7 Nicotinic Acetylcholine Receptors in the Brain: Design, Synthesis, and in Vivo Evaluation of a Dibenzothiophene-Based Radioligand. Molecules 2015, 20: 18387-18421. PMID: 26473809, PMCID: PMC6332508, DOI: 10.3390/molecules201018387.Peer-Reviewed Original ResearchMeSH KeywordsAlpha7 Nicotinic Acetylcholine ReceptorAnimalsAza CompoundsBrainBrain MappingFluorine RadioisotopesHaplorhiniHumansHydrogen BondingKineticsLigandsOxidesPiperazinesPositron-Emission TomographyProtein BindingRadiopharmaceuticalsRatsReceptors, Serotonin, 5-HT3Structure-Activity RelationshipSwineThiophenesTissue DistributionConceptsStructure-activity relationshipsCationic centerPositron emission tomographyHydrogen bond acceptor functionalitiesNicotinic acetylcholine receptorsAcceptor functionalitiesAcetylcholine receptorsNew ligandsDibenzothiophene dioxideΑ7 nicotinic acetylcholine receptorCompound 7Promising PET tracerNew basic structureRadioligand displacement studiesTwo-tissue compartment modelLigandsEmission tomographyPET radioligandKinetic analysisFurther evaluationDynamic positron emission tomographyPET tracersInitial evaluationVivo evaluationBrainMeasurement 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 compoundsRadiotracerKdBrainstemImaging the Cannabinoid CB1 Receptor in Humans with [11C] OMAR: Assessment of Kinetic Analysis Methods, Test–Retest Reproducibility, and Gender Differences
Normandin MD, Zheng MQ, Lin KS, Mason NS, Lin SF, Ropchan J, Labaree D, Henry S, Williams WA, Carson RE, Neumeister A, Huang Y. Imaging the Cannabinoid CB1 Receptor in Humans with [11C] OMAR: Assessment of Kinetic Analysis Methods, Test–Retest Reproducibility, and Gender Differences. Cerebrovascular And Brain Metabolism Reviews 2015, 35: 1313-1322. PMID: 25833345, PMCID: PMC4528005, DOI: 10.1038/jcbfm.2015.46.Peer-Reviewed Original ResearchConceptsTest-retest reliabilityCannabinoid type 1 receptorType 1 receptorCannabinoid CB1 receptorsPositron emission tomography (PET) imagingTest-retest reproducibilityEmission Tomography ImagingGender differencesTwo-tissue compartment modelCerebral uptakePresent studyCB1 receptorsCB1R availabilityInjected doseVascular componentBody weightReceptor availabilityNeuropsychiatric disordersMultilinear analysis methodRegional volumesReceptor bindingTomography imagingParent fractionOne-tissueHuman subjectsTest–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
Radiolabeling of Poly(lactic-co-glycolic acid) (PLGA) Nanoparticles with Biotinylated F‑18 Prosthetic Groups and Imaging of Their Delivery to the Brain with Positron Emission Tomography
Sirianni RW, Zheng MQ, Patel TR, Shafbauer T, Zhou J, Saltzman WM, Carson RE, Huang Y. Radiolabeling of Poly(lactic-co-glycolic acid) (PLGA) Nanoparticles with Biotinylated F‑18 Prosthetic Groups and Imaging of Their Delivery to the Brain with Positron Emission Tomography. Bioconjugate Chemistry 2014, 25: 2157-2165. PMID: 25322194, PMCID: PMC4275164, DOI: 10.1021/bc500315j.Peer-Reviewed Original ResearchConceptsDetection of avidinFate of nanoparticlesAvidin-biotin interactionProsthetic groupNanoparticle deliveryPolymer nanoparticlesNanoparticlesBiotinylated moleculesNoncovalent linkageConvection-enhanced deliveryAvailable biotinHigh purityAvidinBiotinDeliveryFluorobenzylamineSpecific activityFunction of timeMoleculesDerivativesPositron emission tomographySubstratePurityDirect observationKineticsEvaluation of [18F]-(-)-norchlorofluorohomoepibatidine ([18F]-(-)-NCFHEB) as a PET radioligand to image the nicotinic acetylcholine receptors in non-human primates
Bois F, Gallezot JD, Zheng MQ, Lin SF, Esterlis I, Cosgrove KP, Carson RE, Huang Y. Evaluation of [18F]-(-)-norchlorofluorohomoepibatidine ([18F]-(-)-NCFHEB) as a PET radioligand to image the nicotinic acetylcholine receptors in non-human primates. Nuclear Medicine And Biology 2014, 42: 570-577. PMID: 25858513, PMCID: PMC4441617, DOI: 10.1016/j.nucmedbio.2014.08.003.Peer-Reviewed Original ResearchConceptsRhesus monkeysGood test-retest reproducibilityML/Plasma free fractionReceptor binding profileNicotinic acetylcholine receptorsTest-retest reproducibilityNon-human primatesReceptor radiotracerΑ4β2 receptorsFrontal cortexPET examinationsMonkey brainAcetylcholine receptorsBrain regionsDistribution volumePET radioligandMultilinear analysis methodPharmacokinetic propertiesEnd of synthesisNon-displaceable distribution volumeFree fractionPET measurementsMonkeysEvaluation 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 modelsPhosphodiesterase 10A PET Radioligand Development Program: From Pig to Human
Plisson C, Weinzimmer D, Jakobsen S, Natesan S, Salinas C, Lin SF, Labaree D, Zheng MQ, Nabulsi N, Marques TR, Kapur S, Kawanishi E, Saijo T, Gunn RN, Carson RE, Rabiner EA. Phosphodiesterase 10A PET Radioligand Development Program: From Pig to Human. Journal Of Nuclear Medicine 2014, 55: 595-601. PMID: 24614221, DOI: 10.2967/jnumed.113.131409.Peer-Reviewed Original ResearchConceptsMP-10Primate brainRadioligand candidatesBaseline PET studyFirst human administrationTissue kineticsNonhuman primate brainRegional binding potentialSelective PDE10A inhibitorDose-dependent mannerOutcome measuresPreclinical studiesBrain regionsFurther evaluationPET studiesPig brainPET tracersPDE10A inhibitorsBrainVivo studiesReference tissueHuman administrationHuman brainAdministrationGood radiochemical yieldRelationship Between Glycine Transporter 1 Inhibition as Measured with Positron Emission Tomography and Changes in Cognitive Performances in Nonhuman Primates
Castner SA, Murthy NV, Ridler K, Herdon H, Roberts BM, Weinzimmer DP, Huang Y, Zheng MQ, Rabiner EA, Gunn RN, Carson RE, Williams GV, Laruelle M. Relationship Between Glycine Transporter 1 Inhibition as Measured with Positron Emission Tomography and Changes in Cognitive Performances in Nonhuman Primates. Neuropsychopharmacology 2014, 39: 2742-2749. PMID: 24487737, PMCID: PMC4200505, DOI: 10.1038/npp.2014.4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzamidesBrainCarbon RadioisotopesCentral Nervous System AgentsExcitatory Amino Acid AntagonistsFemaleGlycine Plasma Membrane Transport ProteinsKetamineMacaca mulattaMaleMemory, Short-TermNeuropsychological TestsN-MethylaspartatePositron-Emission TomographyRadiopharmaceuticalsSpatial MemoryTetrahydronaphthalenesConceptsOrg 25935GlyT-1 inhibitorsNMDA hypofunctionN-methyl-D-aspartate receptorsPotential therapeutic effectsTreatment of schizophreniaPositron emission tomography (PET) radiotracerPositron emission tomographyNMDA transmissionGlutamatergic transmissionControl conditionKetamine administrationNMDA receptorsTherapeutic effectExtracellular glycineExtracellular levelsGlyT-1Emission tomographyMemory deficitsRhesus monkeysTomography radiotracerNonhuman primatesLines of evidenceHypofunctionCognitive performance
2013
Imaging Nicotine- and Amphetamine-Induced Dopamine Release in Rhesus Monkeys with [11C]PHNO vs [11C]raclopride PET
Gallezot JD, Kloczynski T, Weinzimmer D, Labaree D, Zheng MQ, Lim K, Rabiner EA, Ridler K, Pittman B, Huang Y, Carson RE, Morris ED, Cosgrove KP. Imaging Nicotine- and Amphetamine-Induced Dopamine Release in Rhesus Monkeys with [11C]PHNO vs [11C]raclopride PET. Neuropsychopharmacology 2013, 39: 866-874. PMID: 24220025, PMCID: PMC3924521, DOI: 10.1038/npp.2013.286.Peer-Reviewed Original ResearchConceptsAmphetamine-induced DA releaseD2/D3 receptorsDA releaseD3 receptorsRhesus monkeysAmphetamine-Induced Dopamine ReleaseDopamine D2/D3 receptorsHuman tobacco smokersAmphetamine-induced changesClinical neuroimaging studiesAdult rhesus monkeysPositron emission tomography (PET) imagingEmission Tomography ImagingLow-affinity receptorsNon-human primatesTobacco smokersSubstantia nigraGlobus pallidusDopamine releaseNucleus accumbensNicotineNeuroimaging studiesTomography imagingBPNDReceptorsDetermination of the In Vivo Selectivity of a New κ-Opioid Receptor Antagonist PET Tracer 11C-LY2795050 in the Rhesus Monkey
Kim SJ, Zheng MQ, Nabulsi N, Labaree D, Ropchan J, Najafzadeh S, Carson RE, Huang Y, Morris ED. Determination of the In Vivo Selectivity of a New κ-Opioid Receptor Antagonist PET Tracer 11C-LY2795050 in the Rhesus Monkey. Journal Of Nuclear Medicine 2013, 54: 1668-1674. PMID: 23918735, PMCID: PMC5824998, DOI: 10.2967/jnumed.112.118877.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzamidesBrainComputer SimulationImage Interpretation, Computer-AssistedMacaca mulattaMetabolic Clearance RateModels, BiologicalPositron-Emission TomographyPyrrolidinesRadiopharmaceuticalsReceptors, Opioid, kappaReproducibility of ResultsSensitivity and SpecificityTissue DistributionElevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: a positron emission tomography study
Neumeister A, Normandin MD, Pietrzak RH, Piomelli D, Zheng MQ, Gujarro-Anton A, Potenza MN, Bailey CR, Lin SF, Najafzadeh S, Ropchan J, Henry S, Corsi-Travali S, Carson RE, Huang Y. Elevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: a positron emission tomography study. Molecular Psychiatry 2013, 18: 1034-1040. PMID: 23670490, PMCID: PMC3752332, DOI: 10.1038/mp.2013.61.Peer-Reviewed Original ResearchMeSH KeywordsAdultAmidesAnalysis of VarianceArachidonic AcidsBrainEndocannabinoidsEthanolaminesFemaleGlyceridesHumansHydrocortisoneImidazolesLogistic ModelsMalePalmitic AcidsPiperidinesPolyunsaturated AlkamidesPyrazolesRadionuclide ImagingReceptor, Cannabinoid, CB1Stress Disorders, Post-TraumaticYoung AdultConceptsPost-traumatic stress disorderVolume of distributionCB1 receptor availabilityPositron emission tomographyHC groupReceptor availabilityTC groupCannabinoid type 1 receptorStress disorderPositron emission tomography studyEvidence-based pharmacotherapyEtiology of PTSDType 1 receptorEmission tomography studiesAnandamide concentrationsElevated brainPeripheral levelsHealthy controlsCB1 receptorsUntreated individualsPET scansAnimal modelsCortisol levelsLifetime historyEmission tomographyDirect, Quantitative, and Noninvasive Imaging of the Transport of Active Agents Through Intact Brain with Positron Emission Tomography
Sirianni RW, Zheng MQ, Saltzman WM, Huang Y, Carson RE. Direct, Quantitative, and Noninvasive Imaging of the Transport of Active Agents Through Intact Brain with Positron Emission Tomography. Molecular Imaging And Biology 2013, 15: 596-605. PMID: 23624949, PMCID: PMC3942322, DOI: 10.1007/s11307-013-0636-9.Peer-Reviewed Original ResearchSynthesis and Evaluation of 11C-LY2795050 as a κ-Opioid Receptor Antagonist Radiotracer for PET Imaging
Zheng MQ, Nabulsi N, Kim SJ, Tomasi G, Lin SF, Mitch C, Quimby S, Barth V, Rash K, Masters J, Navarro A, Seest E, Morris ED, Carson RE, Huang Y. Synthesis and Evaluation of 11C-LY2795050 as a κ-Opioid Receptor Antagonist Radiotracer for PET Imaging. Journal Of Nuclear Medicine 2013, 54: 455-463. PMID: 23353688, PMCID: PMC3775344, DOI: 10.2967/jnumed.112.109512.Peer-Reviewed Original ResearchConceptsKappa-opioid receptorsAntagonist radiotracersSelective kappa opioid receptorPET imagingKOR knockout micePathophysiology of depressionSelective KOR antagonistRadioligand competition binding assaysEx vivo analysisDose-dependent mannerFavorable pharmacokinetic propertiesFull antagonist activityKOR antagonistsPeripheral metabolismKOR agonistsTracer candidatesLY2795050Sprague-DawleyAntagonist tracersKnockout miceSpecific binding signalsCompetition binding assaysRhesus monkeysPharmacokinetic propertiesAntagonist activity