2020
The rate of dasotraline brain entry is slow following intravenous administration
Lew R, Constantinescu CC, Holden D, Carson RE, Carroll V, Galluppi G, Koblan KS, Hopkins SC. The rate of dasotraline brain entry is slow following intravenous administration. Psychopharmacology 2020, 237: 3435-3446. PMID: 32813030, PMCID: PMC7651685, DOI: 10.1007/s00213-020-05623-8.Peer-Reviewed Original ResearchConceptsSynaptic dopamine levelsDopamine levelsDAT occupancyPositron emission tomographyIntravenous administrationSynaptic dopamineRhesus monkeysSlow oral absorptionNorepinephrine reuptake inhibitorsBlood-brain barrierHalf-maximal displacementDopamine transporter inhibitionRecreational drug abusersBrain entryResultsIntravenous administrationReuptake inhibitorsPharmacodynamic effectsD2 receptorsRaclopride bindingAssociated elevationDasotralineDrug abusersMethylphenidateTransporter inhibitionEmission tomography
2019
Synthesis and in vivo evaluation of [18F]UCB-J for PET imaging of synaptic vesicle glycoprotein 2A (SV2A)
Li S, Cai Z, Zhang W, Holden D, Lin SF, Finnema SJ, Shirali A, Ropchan J, Carre S, Mercier J, Carson RE, Nabulsi N, Huang Y. Synthesis and in vivo evaluation of [18F]UCB-J for PET imaging of synaptic vesicle glycoprotein 2A (SV2A). European Journal Of Nuclear Medicine And Molecular Imaging 2019, 46: 1952-1965. PMID: 31175396, PMCID: PMC6810698, DOI: 10.1007/s00259-019-04357-w.Peer-Reviewed Original ResearchConceptsSynaptic vesicle glycoprotein 2AHigh specific binding signalsNonhuman primatesPET imagingHigh brain uptakeRegional distribution volumesBrain uptakeSynaptic densityOne-tissue compartment modelExcellent imaging agentRegional time-activity curvesVivo biomarkersArterial samplesSpecific binding signalsPsychiatric diseasesTime-activity curvesAlzheimer's diseaseDistribution volumeNeuropsychiatric disordersRadioactive metabolitesRhesus monkeysPET radiotracersVivo evaluationDiseaseImaging agentImaging histamine H3 receptors with [18F]FMH3: Test–retest and occupancy studies in the non‐human primate
Sandiego CM, Barret O, Lee H, Alagille D, Amenta A, Fowles K, Holden D, Seibyl JP, Tamagnan G. Imaging histamine H3 receptors with [18F]FMH3: Test–retest and occupancy studies in the non‐human primate. Synapse 2019, 73: e22096. PMID: 30835877, DOI: 10.1002/syn.22096.Peer-Reviewed Original ResearchConceptsABT-239Non-human primatesClinical investigationPositron emission tomography radioligandVolume of distributionReceptor subtype 3Histamine H3 receptorsDose-dependent effectAdult female baboonsPET brain scansBrain stemPlasma levelsSleep abnormalitiesBaseline scanH3 receptorsTomography radioligandOccupancy studiesCognitive disordersSubtype 3Brain scansBrain regionsCortical regionsPET studiesCiproxifanBaseline V
2017
Evaluation of the Lysophosphatidic Acid Receptor Type 1 Radioligand 11C-BMT-136088 for Lung Imaging in Rhesus Monkeys
Gallezot JD, Nabulsi NB, Holden D, Lin SF, Labaree D, Ropchan J, Najafzadeh S, Donnelly DJ, Cao K, Bonacorsi S, Seiders J, Roppe J, Hayes W, Huang Y, Du S, Carson RE. Evaluation of the Lysophosphatidic Acid Receptor Type 1 Radioligand 11C-BMT-136088 for Lung Imaging in Rhesus Monkeys. Journal Of Nuclear Medicine 2017, 59: 327-333. PMID: 28864634, DOI: 10.2967/jnumed.117.195073.Peer-Reviewed Original ResearchConceptsMultilinear analysis 1Rhesus monkeysHighest organ doseLung tissue injuryLung regionsΜSv/MBqPlasma free fractionReceptor type 1Test-retest scansTest-retest variabilityVivo dissociationMolecule lysophosphatidic acidRight lung regionsML of plasmaNondisplaceable volumePulmonary fibrosisLung fibrosisVascular leakageInfusion protocolPlasma concentrationsTissue injuryDrug doseNormal healingOrgan doseType 1PET 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 ResearchA multi species evaluation of the radiation dosimetry of [11C]erlotinib, the radiolabeled analog of a clinically utilized tyrosine kinase inhibitor
Petrulli JR, Hansen SB, Abourbeh G, Yaqub M, Bahce I, Holden D, Huang Y, Nabulsi NB, Contessa JN, Mishani E, Lammertsma AA, Morris ED. A multi species evaluation of the radiation dosimetry of [11C]erlotinib, the radiolabeled analog of a clinically utilized tyrosine kinase inhibitor. Nuclear Medicine And Biology 2017, 47: 56-61. PMID: 28126682, PMCID: PMC5360653, DOI: 10.1016/j.nucmedbio.2016.12.009.Peer-Reviewed Original ResearchConceptsTyrosine kinase inhibitorsTime-activity curvesEquivalent doseNon-small cell lung cancer patientsStage IIIA NSCLC patientsEpidermal growth factor receptor (EGFR) mutationsCell lung cancer patientsCritical organsKinase inhibitorsIIIA NSCLC patientsLung cancer patientsHighest equivalent doseTime-integrated activity coefficientsWhole bodyMean equivalent dosesRhesus macaque monkeysNSCLC patientsDosimetry profileCancer patientsGallbladder wallReceptor mutationsMacaque monkeysIdentifiable organsInjected activityEffective doseThe Search for a Subtype-Selective PET Imaging Agent for the GABAA Receptor Complex: Evaluation of the Radiotracer [11C]ADO in Nonhuman Primates
Lin SF, Bois F, Holden D, Nabulsi N, Pracitto R, Gao H, Kapinos M, Teng JK, Shirali A, Ropchan J, Carson RE, Elmore CS, Vasdev N, Huang Y. The Search for a Subtype-Selective PET Imaging Agent for the GABAA Receptor Complex: Evaluation of the Radiotracer [11C]ADO in Nonhuman Primates. Molecular Imaging 2017, 16: 1536012117731258. PMID: 28929924, PMCID: PMC5912275, DOI: 10.1177/1536012117731258.Peer-Reviewed Original ResearchConceptsNonhuman primatesNovel positron emission tomography (PET) radiotracerAbsolute test-retest variabilityFast tissue kineticsSubtype-selective GABATissue kineticsHigh brain uptakeGABAA receptor complexRegional binding potentialPositron emission tomography (PET) radiotracerPET imaging agentRegional distribution volumesTest-retest variabilityNondisplaceable volumeUndesirable side effectsRegion-specific distributionΓ-amino butyric acidAnticonvulsive effectBrain uptakeAnxiolytic effectsMinutes postinjectionOne-tissue compartment modelGABA sitesStriatal regionsRegional time-activity curves
2016
Imaging synaptic density in the living human brain
Finnema SJ, Nabulsi NB, Eid T, Detyniecki K, Lin SF, Chen MK, Dhaher R, Matuskey D, Baum E, Holden D, Spencer DD, Mercier J, Hannestad J, Huang Y, Carson RE. Imaging synaptic density in the living human brain. Science Translational Medicine 2016, 8: 348ra96. PMID: 27440727, DOI: 10.1126/scitranslmed.aaf6667.Peer-Reviewed Original ResearchConceptsSynaptic densityPositron emission tomographyPET imagingSynaptic vesicle glycoprotein 2ATemporal lobe epilepsyNumerous brain disordersCentral nervous systemNumber of synapsesJ PET imagingHuman brainHuman PET studiesPredominant neuronsSurgical resectionSynaptic lossLobe epilepsyPsychiatric disordersNervous systemBrain disordersPresynaptic boutonsAlzheimer's diseaseBrain tissueEmission tomographyNeuron contactsTherapeutic monitoringPET studiesIncreased 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 loopChemotherapyMalignancySynthesis and Preclinical Evaluation of 11C-UCB-J as a PET Tracer for Imaging the Synaptic Vesicle Glycoprotein 2A in the Brain
Nabulsi N, Mercier J, Holden D, Carré S, Najafzadeh S, Vandergeten MC, Lin SF, Deo A, Price N, Wood M, Lara-Jaime T, Montel F, Laruelle M, Carson RE, Hannestad J, Huang Y. Synthesis and Preclinical Evaluation of 11C-UCB-J as a PET Tracer for Imaging the Synaptic Vesicle Glycoprotein 2A in the Brain. Journal Of Nuclear Medicine 2016, 57: 777-784. PMID: 26848175, DOI: 10.2967/jnumed.115.168179.Peer-Reviewed Original ResearchConceptsSynaptic vesicle glycoprotein 2AWhole-body biodistributionPET radiotracersNonhuman primatesDose-limiting organHigher free fractionGray matter regionsBaseline VTNondisplaceable distribution volumeAntiepileptic drugsVitro inhibition constantSynaptic densityPreclinical evaluationMonkey brainDistribution volumeArterial samplingEndocrine cellsRegional volumesMatter regionsRhesus macaquesPET tracersUCBFree fractionBrainTarget occupancyComparative 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 tissue
2014
Evaluation of 11C-BU99008, a PET Ligand for the Imidazoline2 Binding Sites in Rhesus Brain
Parker CA, Nabulsi N, Holden D, Lin SF, Cass T, Labaree D, Kealey S, Gee AD, Husbands SM, Quelch D, Carson RE, Nutt DJ, Huang Y, Tyacke RJ. Evaluation of 11C-BU99008, a PET Ligand for the Imidazoline2 Binding Sites in Rhesus Brain. Journal Of Nuclear Medicine 2014, 55: 838-844. PMID: 24711648, DOI: 10.2967/jnumed.113.131854.Peer-Reviewed Original ResearchIn Vivo Evaluation of 18F-MNI698: An 18F-Labeled Radiotracer for Imaging of Serotonin 4 Receptors in Brain
Tavares AA, Caillé F, Barret O, Papin C, Lee H, Morley TJ, Fowles K, Holden D, Seibyl JP, Alagille D, Tamagnan GD. In Vivo Evaluation of 18F-MNI698: An 18F-Labeled Radiotracer for Imaging of Serotonin 4 Receptors in Brain. Journal Of Nuclear Medicine 2014, 55: 858-864. PMID: 24686782, DOI: 10.2967/jnumed.113.132712.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainBrain MappingDioxanesDose-Response Relationship, RadiationFemaleFluorine RadioisotopesImage Processing, Computer-AssistedKineticsMacaca mulattaMalePiperidinesPositron-Emission TomographyRadiopharmaceuticalsReceptors, Serotonin, 5-HT4Reproducibility of ResultsSerotonin AntagonistsTime FactorsTissue DistributionConceptsBrain disordersPET radiotracersSerotonin 4 receptorBolus intravenous injectionNovel therapeutic approachesMultiple brain disordersAdult rhesus monkeysDifferent brain disordersDose limitDose-dependent mannerPromising PET radiotracerTest-retest variabilityTest-retest measurementsRadiotracer infusionBrain distributionBolus injectionIntravenous injectionArterial bloodTherapeutic approachesHuman studiesBody weightConstant infusionMonkey brainDistribution volumeInvasive methodWhole-body biodistribution and dosimetry estimates of a novel radiotracer for imaging of serotonin 4 receptors in brain: [18F]MNI-698
Tavares AA, Caillé F, Barret O, Papin C, Lee H, Morley TJ, Fowles K, Holden D, Seibyl JP, Alagille D, Tamagnan GD. Whole-body biodistribution and dosimetry estimates of a novel radiotracer for imaging of serotonin 4 receptors in brain: [18F]MNI-698. Nuclear Medicine And Biology 2014, 41: 432-439. PMID: 24674817, DOI: 10.1016/j.nucmedbio.2014.02.005.Peer-Reviewed Original ResearchConceptsSerotonin 4 receptorWhole-body biodistributionUrinary bladderDosimetry estimatesOLINDA/EXM 1.0 softwareNovel radiotracersEffective doseMSv/MBqIntravenous bolus injectionWhole-body positron emission tomography (PET) imagesHuman clinical trialsFuture clinical protocolsMain elimination routeAdult rhesus monkeysUrinary bladder modelWhole body weightClinical trialsBolus injectionClinical protocolsNew radiotracersRhesus monkeysCritical organsEffective dosesEmission tomography imagesBladder model