2020
Feasibility study of PET dynamic imaging of [18F]DHMT for quantification of reactive oxygen species in the myocardium of large animals
Wu J, Boutagy NE, Cai Z, Lin SF, Zheng MQ, Feher A, Stendahl JC, Kapinos M, Gallezot JD, Liu H, Mulnix T, Zhang W, Lindemann M, Teng JK, Miller EJ, Huang Y, Carson RE, Sinusas AJ, Liu C. Feasibility study of PET dynamic imaging of [18F]DHMT for quantification of reactive oxygen species in the myocardium of large animals. Journal Of Nuclear Cardiology 2020, 29: 216-225. PMID: 32415628, PMCID: PMC7666654, DOI: 10.1007/s12350-020-02184-3.Peer-Reviewed Original ResearchAnimalsDogsFeasibility StudiesHumansMyocardiumPositron-Emission TomographyReactive Oxygen SpeciesSuperoxidesSeparating 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
2018
High Single Doses of Radiation May Induce Elevated Levels of Hypoxia in Early-Stage Non-Small Cell Lung Cancer Tumors
Kelada OJ, Decker RH, Nath SK, Johung KL, Zheng MQ, Huang Y, Gallezot JD, Liu C, Carson RE, Oelfke U, Carlson DJ. High Single Doses of Radiation May Induce Elevated Levels of Hypoxia in Early-Stage Non-Small Cell Lung Cancer Tumors. International Journal Of Radiation Oncology • Biology • Physics 2018, 102: 174-183. PMID: 30102194, PMCID: PMC6092043, DOI: 10.1016/j.ijrobp.2018.05.032.Peer-Reviewed Original ResearchMeSH KeywordsAgedCarcinoma, Non-Small-Cell LungCohort StudiesDose-Response Relationship, RadiationFemaleHumansLung NeoplasmsMaleNeoplasm StagingPositron-Emission TomographyRadiosurgeryTumor HypoxiaConceptsStereotactic body radiation therapyTumor hypoxic volumeHigh single dosesNon-small cell lung cancer (NSCLC) tumorsCell lung cancer tumorsLung cancer tumorsSingle dosesTumor hypoxiaTreatment failureNSCLC tumorsBlood ratioHypoxic volumeRadiation therapyDay 2F-fluoromisonidazole (FMISO) positron emission tomographyCancer tumorsInstitutional review board-approved studyTumor vascular responseBody radiation therapyBoard-approved studyConventional radiation therapyPositron emission tomographyBaseline hypoxiaDetectable hypoxiaNSCLC patients
2017
Novel 18F-Labeled κ-Opioid Receptor Antagonist as PET Radiotracer: Synthesis and In Vivo Evaluation of 18F-LY2459989 in Nonhuman Primates
Li S, Cai Z, Zheng MQ, Holden D, Naganawa M, Lin SF, Ropchan J, Labaree D, Kapinos M, Lara-Jaime T, Navarro A, Huang Y. Novel 18F-Labeled κ-Opioid Receptor Antagonist as PET Radiotracer: Synthesis and In Vivo Evaluation of 18F-LY2459989 in Nonhuman Primates. Journal Of Nuclear Medicine 2017, 59: 140-146. PMID: 28747521, PMCID: PMC5750518, DOI: 10.2967/jnumed.117.195586.Peer-Reviewed Original ResearchConceptsPET radiotracersNonhuman primatesTime-activity curvesHigh specific binding signalsΚ-opioid receptor antagonistCentral nervous system disordersFast tissue kineticsBrain time-activity curvesCaudate/putamenNervous system disordersΚ-opioid receptorsRegional binding potentialPeak uptake timeRegional distribution volumesAntagonist radiotracersReceptor antagonistFrontal cortexNovel 18FRegional time-activity curvesSystem disordersNovel radioligandPET scansSpecific binding signalsTemporal cortexMonkey brainQuantification of Tumor Hypoxic Fractions Using Positron Emission Tomography with [18F]Fluoromisonidazole ([18F]FMISO) Kinetic Analysis and Invasive Oxygen Measurements
Kelada OJ, Rockwell S, Zheng MQ, Huang Y, Liu Y, Booth CJ, Decker RH, Oelfke U, Carson RE, Carlson DJ. Quantification of Tumor Hypoxic Fractions Using Positron Emission Tomography with [18F]Fluoromisonidazole ([18F]FMISO) Kinetic Analysis and Invasive Oxygen Measurements. Molecular Imaging And Biology 2017, 19: 893-902. PMID: 28409339, PMCID: PMC5640490, DOI: 10.1007/s11307-017-1083-9.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell HypoxiaCell Line, TumorHumansKineticsMaleMice, Inbred BALB CMisonidazoleMusclesNeoplasmsOxygenPositron-Emission TomographyTomography, X-Ray ComputedTumor BurdenConceptsPositron emission tomographyTumor hypoxic fractionHypoxic fractionEmission tomographyLung cancer radiotherapy patientsPO2 measurementsAbsolute tumor volumeC miceDirect pO2 measurementsBlood ratioClinical impactTumor volumeHypoxia quantificationSubcutaneous tumorsPurposeThe purposeTracer kinetic modelingRadiotherapy patientsPET imagingPatientsPO2 valuesScansPatlak modelTomographyTwo-compartmentTBRPET imaging of α7 nicotinic acetylcholine receptors: a comparative study of [18F]ASEM and [18F]DBT-10 in nonhuman primates, and further evaluation of [18F]ASEM in humans
Hillmer AT, Li S, Zheng MQ, Scheunemann M, Lin SF, Nabulsi N, Holden D, Pracitto R, Labaree D, Ropchan J, Teodoro R, Deuther-Conrad W, Esterlis I, Cosgrove KP, Brust P, Carson RE, Huang Y. PET imaging of α7 nicotinic acetylcholine receptors: a comparative study of [18F]ASEM and [18F]DBT-10 in nonhuman primates, and further evaluation of [18F]ASEM in humans. European Journal Of Nuclear Medicine And Molecular Imaging 2017, 44: 1042-1050. PMID: 28120003, PMCID: PMC5400702, DOI: 10.1007/s00259-017-3621-8.Peer-Reviewed Original Research
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 ResearchMeSH KeywordsAdultBenzamidesBrainCarbon RadioisotopesHumansMaleMiddle AgedPositron-Emission TomographyPyrrolidinesReceptors, Opioid, kappaYoung AdultConceptsHours 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 ResearchMeSH KeywordsAdolescentAdultAgedBrainCarbon IsotopesCerebral AngiographyFemaleHumansMaleMiddle AgedPositron-Emission TomographyRadiopharmaceuticalsReceptor, Cannabinoid, CB1Sex CharacteristicsConceptsTest-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 subjectsSynthesis of [18F]FMISO in a flow-through microfluidic reactor: Development and clinical application
Zheng MQ, Collier L, Bois F, Kelada OJ, Hammond K, Ropchan J, Akula MR, Carlson DJ, Kabalka GW, Huang Y. Synthesis of [18F]FMISO in a flow-through microfluidic reactor: Development and clinical application. Nuclear Medicine And Biology 2015, 42: 578-584. PMID: 25779036, DOI: 10.1016/j.nucmedbio.2015.01.010.Peer-Reviewed Original ResearchTest–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 observationKineticsAssociation of In Vivo κ-Opioid Receptor Availability and the Transdiagnostic Dimensional Expression of Trauma-Related Psychopathology
Pietrzak RH, Naganawa M, Huang Y, Corsi-Travali S, Zheng MQ, Stein MB, Henry S, Lim K, Ropchan J, Lin SF, Carson RE, Neumeister A. Association of In Vivo κ-Opioid Receptor Availability and the Transdiagnostic Dimensional Expression of Trauma-Related Psychopathology. JAMA Psychiatry 2014, 71: 1262-1270. PMID: 25229257, DOI: 10.1001/jamapsychiatry.2014.1221.Peer-Reviewed Original ResearchMeSH KeywordsAdultAmygdalaBenzamidesCarbon RadioisotopesCase-Control StudiesCross-Sectional StudiesDepressionFemaleFunctional NeuroimagingGyrus CinguliHumansHydrocortisoneMaleNeural PathwaysPhobic DisordersPositron-Emission TomographyPsychiatric Status Rating ScalesPyrrolidinesReceptors, Opioid, kappaStress Disorders, Post-TraumaticVentral StriatumWounds and InjuriesYoung AdultConceptsUrinary cortisol levelsLoss symptomsTrauma-related psychopathologyCortisol levelsNeural circuitsDynorphin/κ-opioid receptor systemΚ-opioid receptor systemHamilton Depression Rating ScaleRating ScaleAdrenal axis systemClinician-Administered PTSD ScalePositron emission tomography studyDepression Rating ScaleHamilton Rating ScaleMechanism-based treatmentsEmission tomography studiesAcademic medical centerPositron emission tomographyKOR systemPreclinical dataTrauma-exposed adultsHigh-resolution positron emission tomographyMedical CenterMAIN OUTCOMEDepressive symptomsKinetic Modeling of 11C-LY2795050, A Novel Antagonist Radiotracer for PET Imaging of the Kappa Opioid Receptor in Humans
Naganawa M, Zheng MQ, Nabulsi N, Tomasi G, Henry S, Lin SF, Ropchan J, Labaree D, Tauscher J, Neumeister A, Carson RE, Huang Y. Kinetic Modeling of 11C-LY2795050, A Novel Antagonist Radiotracer for PET Imaging of the Kappa Opioid Receptor in Humans. Cerebrovascular And Brain Metabolism Reviews 2014, 34: 1818-1825. PMID: 25182664, PMCID: PMC4269759, DOI: 10.1038/jcbfm.2014.150.Peer-Reviewed Original ResearchConceptsKappa-opioid receptorsMultilinear analysis 1Opioid receptorsNovel kappa opioid receptorDistribution volumePositron emission tomography (PET) imagingEmission Tomography ImagingLow intersubject variabilityTwo-tissue compartment modelAntagonist radiotracersOral naltrexoneNondisplaceable distribution volumeBaseline scanLY2795050Human studiesArterial input functionPET imagingTomography imagingIntersubject variabilityNaltrexoneEvaluation 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 measurementsMonkeys