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 agentEvaluation of 11C-LSN3172176 as a Novel PET Tracer for Imaging M1 Muscarinic Acetylcholine Receptors in Nonhuman Primates
Nabulsi NB, Holden D, Zheng MQ, Bois F, Lin SF, Najafzadeh S, Gao H, Ropchan J, Lara-Jaime T, Labaree D, Shirali A, Slieker L, Jesudason C, Barth V, Navarro A, Kant N, Carson RE, Huang Y. Evaluation of 11C-LSN3172176 as a Novel PET Tracer for Imaging M1 Muscarinic Acetylcholine Receptors in Nonhuman Primates. Journal Of Nuclear Medicine 2019, 60: 1147-1153. PMID: 30733324, DOI: 10.2967/jnumed.118.222034.Peer-Reviewed Original ResearchConceptsMuscarinic acetylcholine receptorsAcetylcholine receptorsNonhuman primatesM1 muscarinic acetylcholine receptorBrain time-activity curvesRich brain regionsArterial blood samplingNovel PET tracersSuitable reference regionRegional distribution volumesReference regionDevelopment of drugsBrain uptakeGlobus pallidusDistribution volume valuesNucleus accumbensBlood samplingPET scansTime-activity curvesCognitive impairmentAlzheimer's diseaseBrain regionsDistribution volumeSelective radiotracerRhesus monkeys
2018
Synthesis and in Vivo Evaluation of a Novel PET Radiotracer for Imaging of Synaptic Vesicle Glycoprotein 2A (SV2A) in Nonhuman Primates
Li S, Cai Z, Wu X, Holden D, Pracitto R, Kapinos M, Gao H, Labaree D, Nabulsi N, Carson RE, Huang Y. Synthesis and in Vivo Evaluation of a Novel PET Radiotracer for Imaging of Synaptic Vesicle Glycoprotein 2A (SV2A) in Nonhuman Primates. ACS Chemical Neuroscience 2018, 10: 1544-1554. PMID: 30396272, PMCID: PMC6810685, DOI: 10.1021/acschemneuro.8b00526.Peer-Reviewed Original ResearchConceptsSynaptic vesicle glycoprotein 2AStandardized uptake valuePET radiotracersNonhuman primatesAlterations of synapsesC-UCBPeak standardized uptake valueVivo evaluationHigh brain uptakeNovel PET radiotracersBrain uptakeSynaptic densityExcellent radiotracerPsychiatric disordersUptake valueCingulate cortexAlzheimer's diseaseBrain disordersNovel radiotracersRhesus monkeysNeurodegenerative diseasesTissue kineticsDiseaseAttractive imaging propertiesLevetiracetam
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 Evaluation of Four σ1 Radiotracers in Nonhuman Primates
Baum E, Cai Z, Bois F, Holden D, Lin SF, Lara-Jaime T, Kapinos M, Chen Y, Deuther-Conrad W, Fischer S, Dukic-Stefanovic S, Bunse P, Wünsch B, Brust P, Jia H, Huang Y. PET Imaging Evaluation of Four σ1 Radiotracers in Nonhuman Primates. Journal Of Nuclear Medicine 2017, 58: 982-988. PMID: 28232607, DOI: 10.2967/jnumed.116.188052.Peer-Reviewed Original ResearchConceptsImaging evaluationHigh specific binding signalsRhesus monkeysFast tissue kineticsAdult male rhesus monkeysHigh brain uptakeMale rhesus monkeysBrain uptakeDistribution volume valuesBaseline scanRhesus brainVariety of diseasesSpecific binding signalsTime-activity curvesCingulate cortexAlzheimer's diseaseBrain regionsDistribution volumeRadiotracer bindingArterial input functionPET radiotracersPET tracersNonhuman primatesSame monkeysTissue kinetics
2014
Further evaluation of [11C]MP‐10 as a radiotracer for phosphodiesterase 10A: PET imaging study in rhesus monkeys and brain tissue metabolite analysis
Lin S, Labaree D, Chen M, Holden D, Gallezot J, Kapinos M, Teng J, Najafzadeh S, Plisson C, Rabiner EA, Gunn RN, Carson RE, Huang Y. Further evaluation of [11C]MP‐10 as a radiotracer for phosphodiesterase 10A: PET imaging study in rhesus monkeys and brain tissue metabolite analysis. Synapse 2014, 69: 86-95. PMID: 25450608, PMCID: PMC4275380, DOI: 10.1002/syn.21792.Peer-Reviewed Original ResearchConceptsRhesus monkeysPhosphodiesterase 10ASprague-Dawley ratsMP-10Dose-dependent mannerSpecific PET tracersHigh specific bindingPET imaging studiesTissue uptake kineticsBaseline scanBrain regionsImaging studiesFurther evaluationMultilinear analysis methodRegional volumesPET tracersNonhuman primatesPET imagingVivo studiesReference tissueMonkeysBrainCerebellumSpecific bindingPresent studyAn 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 purityWhole-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