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 Research
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 ResearchConceptsPositron 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
Increased Nanoparticle Delivery to Brain Tumors by Autocatalytic Priming for Improved Treatment and Imaging
Han L, Kong DK, Zheng MQ, Murikinati S, Ma C, Yuan P, Li L, Tian D, Cai Q, Ye C, Holden D, Park JH, Gao X, Thomas JL, Grutzendler J, Carson RE, Huang Y, Piepmeier JM, Zhou J. Increased Nanoparticle Delivery to Brain Tumors by Autocatalytic Priming for Improved Treatment and Imaging. ACS Nano 2016, 10: 4209-4218. PMID: 26967254, PMCID: PMC5257033, DOI: 10.1021/acsnano.5b07573.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBiological TransportBlood-Brain BarrierBrain NeoplasmsCell Line, TumorDecanoic AcidsDrug Delivery SystemsEthanolaminesFemaleGenetic TherapyHeterograftsHumansMatrix Metalloproteinase 2MiceMice, Inbred C57BLNanoparticlesOptical ImagingPaclitaxelPermeabilityPolymersPurinesPyrazolesScorpion VenomsTranscytosisTumor MicroenvironmentConceptsBlood-brain barrierLow delivery efficiencyTransport of nanoparticlesCancer gene therapyNanoparticle deliveryMore nanoparticlesBrain tumorsNanoparticlesDelivery efficiencyGene therapySystemic deliveryNPsBrain malignanciesBBB modulatorsPharmacological agentsBrain cancerBrain regionsTumorsDeliveryBrainImproved treatmentInadequate amountsPositive feedback loopChemotherapyMalignancyComparative 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
PET 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 compoundsRadiotracerKdBrainstem
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 measurementsMonkeysAn Improved Antagonist Radiotracer for the κ-Opioid Receptor: Synthesis and Characterization of 11C-LY2459989
Zheng MQ, Kim SJ, Holden D, Lin SF, Need A, Rash K, Barth V, Mitch C, Navarro A, Kapinos M, Maloney K, Ropchan J, Carson RE, Huang Y. An Improved Antagonist Radiotracer for the κ-Opioid Receptor: Synthesis and Characterization of 11C-LY2459989. Journal Of Nuclear Medicine 2014, 55: 1185-1191. PMID: 24854795, PMCID: PMC4826283, DOI: 10.2967/jnumed.114.138701.Peer-Reviewed Original ResearchConceptsHigh specific binding signalsΚ-opioid receptorsSpecific binding signalsPET radioligandRhesus monkeysPromising PET imaging agentSelective KOR antagonistNovel PET radioligandFavorable pharmacokinetic propertiesPET imaging agentMultilinear analysis-1 (MA1) methodAntagonist radiotracersKOR antagonistsPeripheral metabolismGlobus pallidusOpioid receptorsTracer candidatesFrontal cortexArterial input function measurementTemporal cortexCingulate cortexNeuropsychiatric diseasesPharmacokinetic propertiesFull antagonistHigh radiochemical purityPhosphodiesterase 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
Quantitative Analysis of [11C]-Erlotinib PET Demonstrates Specific Binding for Activating Mutations of the EGFR Kinase Domain
Petrulli JR, Sullivan JM, Zheng MQ, Bennett DC, Charest J, Huang Y, Morris ED, Contessa JN. Quantitative Analysis of [11C]-Erlotinib PET Demonstrates Specific Binding for Activating Mutations of the EGFR Kinase Domain. Neoplasia 2013, 15: 1347-1353. PMID: 24403856, PMCID: PMC3884525, DOI: 10.1593/neo.131666.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarbon RadioisotopesCatalytic DomainCell Line, TumorDrug Evaluation, PreclinicalErbB ReceptorsErlotinib HydrochlorideGene ExpressionHumansMiceMice, NudeMutation, MissenseNeoplasm TransplantationPhosphorylationPositron-Emission TomographyProtein BindingProtein Processing, Post-TranslationalQuinazolinesRadiopharmaceuticalsConceptsNon-small cell lung cancerEpidermal growth factor receptorPositron emission tomographyMutant non-small cell lung cancerNovel clinical methodologyCell lung cancerMutations of EGFREGFR mutation statusDomain mutationsHuman cancer xenograftsKinase domain mutationsConstitutive EGFR phosphorylationMultiple tumor typesPET scan analysisMolecular imaging approachesExtracellular domain mutationsWild-type epidermal growth factor receptorSimplified reference tissue modelGrowth factor receptorReference tissue modelNSCLC xenograftsLung cancerCancer xenograftsMalignant gliomasClinical utilityImaging 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 DistributionHighly penetrative, drug-loaded nanocarriers improve treatment of glioblastoma
Zhou J, Patel TR, Sirianni RW, Strohbehn G, Zheng MQ, Duong N, Schafbauer T, Huttner AJ, Huang Y, Carson RE, Zhang Y, Sullivan DJ, Piepmeier JM, Saltzman WM. Highly penetrative, drug-loaded nanocarriers improve treatment of glioblastoma. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 11751-11756. PMID: 23818631, PMCID: PMC3718184, DOI: 10.1073/pnas.1304504110.Peer-Reviewed Original ResearchDirect, 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 ResearchDetermination of In Vivo Bmax and Kd for 11C-GR103545, an Agonist PET Tracer for κ-Opioid Receptors: A Study in Nonhuman Primates
Tomasi G, Nabulsi N, Zheng MQ, Weinzimmer D, Ropchan J, Blumberg L, Brown-Proctor C, Ding YS, Carson RE, Huang Y. Determination of In Vivo Bmax and Kd for 11C-GR103545, an Agonist PET Tracer for κ-Opioid Receptors: A Study in Nonhuman Primates. Journal Of Nuclear Medicine 2013, 54: 600-608. PMID: 23424192, PMCID: PMC3775350, DOI: 10.2967/jnumed.112.112672.Peer-Reviewed Original Research