2023
Preclinical evaluation of a brain penetrant PARP PET imaging probe in rat glioblastoma and nonhuman primates
Chen B, Ojha D, Toyonaga T, Tong J, Pracitto R, Thomas M, Liu M, Kapinos M, Zhang L, Zheng M, Holden D, Fowles K, Ropchan J, Nabulsi N, De Feyter H, Carson R, Huang Y, Cai Z. Preclinical evaluation of a brain penetrant PARP PET imaging probe in rat glioblastoma and nonhuman primates. European Journal Of Nuclear Medicine And Molecular Imaging 2023, 50: 2081-2099. PMID: 36849748, DOI: 10.1007/s00259-023-06162-y.Peer-Reviewed Original ResearchConceptsPositron emission tomographyHealthy nonhuman primatesVolume of distributionDistribution volume ratioBrain kineticsRat glioblastoma modelPreclinical evaluationBrain regionsGlioblastoma modelPET tracersNonhuman primatesTumor-bearing ratsEx vivo biodistributionPET imaging resultsActive clinical trialsTreatment of glioblastomaHigh specific uptakeDynamic PET scansNoninvasive quantificationBrain positron emission tomographyNondisplaceable volumeBrain penetrationLow nonspecific uptakePrognostic informationClinical trials
2020
Dysregulation of Decision Making Related to Metabotropic Glutamate 5, but Not Midbrain D3, Receptor Availability Following Cocaine Self-administration in Rats
Groman SM, Hillmer AT, Liu H, Fowles K, Holden D, Morris ED, Lee D, Taylor JR. Dysregulation of Decision Making Related to Metabotropic Glutamate 5, but Not Midbrain D3, Receptor Availability Following Cocaine Self-administration in Rats. Biological Psychiatry 2020, 88: 777-787. PMID: 32826065, PMCID: PMC8935943, DOI: 10.1016/j.biopsych.2020.06.020.Peer-Reviewed Original ResearchConceptsCocaine-dependent individualsProbabilistic reversalRelapse-like behaviorTest of motivationReceptor availabilityPersistent drug useMetabotropic glutamate 5Neural mechanismsCompulsive patternsDecision-making processDrug-induced adaptationsSelective impairmentDrug useWeeks of abstinenceCocaine takingCocaine Self-AdministrationBrain regionsDegree of disruptionDays of cocaineAdult male ratsCocaine-induced increasesCocaine-induced changesDrug-induced alterationsRobust alterationsPositron emission tomographyMidbrain D3 Receptor Availability Predicts Escalation in Cocaine Self-administration
Groman SM, Hillmer AT, Liu H, Fowles K, Holden D, Morris ED, Lee D, Taylor JR. Midbrain D3 Receptor Availability Predicts Escalation in Cocaine Self-administration. Biological Psychiatry 2020, 88: 767-776. PMID: 32312578, PMCID: PMC8954711, DOI: 10.1016/j.biopsych.2020.02.017.Peer-Reviewed Original ResearchConceptsProbabilistic reversalTests of extinctionSubstance-dependent individualsCue-induced reinstatementRelapse-like behaviorTest of motivationAddiction-like behaviorCocaine self-administration behaviorCocaine-taking behaviorReceptor availabilitySelf-administer cocaineIndividual differencesAddicted populationNeurobiological mechanismsSelf-administration behaviorGreater escalationGreater motivationPoor decisionsNeural adaptationD3 receptor availabilityCocaine Self-AdministrationBehavioral biomarkersDecision-making functionsChoice behaviorRate of escalation
2019
Anti-edema and antioxidant combination therapy for ischemic stroke via glyburide-loaded betulinic acid nanoparticles
Deng G, Ma C, Zhao H, Zhang S, Liu J, Liu F, Chen Z, Chen AT, Yang X, Avery J, Zou P, Du F, Lim KP, Holden D, Li S, Carson RE, Huang Y, Chen Q, Kimberly WT, Simard JM, Sheth KN, Zhou J. Anti-edema and antioxidant combination therapy for ischemic stroke via glyburide-loaded betulinic acid nanoparticles. Theranostics 2019, 9: 6991-7002. PMID: 31660082, PMCID: PMC6815966, DOI: 10.7150/thno.35791.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntioxidantsBetulinic AcidBrain EdemaDrug Delivery SystemsDrug Therapy, CombinationDrugs, Chinese HerbalEucommiaceaeGlyburideHumansMaleMiceMice, Inbred C57BLNanoparticlesPentacyclic TriterpenesPositron Emission Tomography Computed TomographyRatsRats, Sprague-DawleyStrokeTriterpenesConceptsBA nanoparticlesFunctional nanomaterialsMultifunctional nanoparticlesAcid nanoparticlesNanoparticlesSingle-agent pharmacotherapyNanomaterialsDrug deliveryCombination therapyComplementary targetTherapeutic benefitPositron emission tomography-computed tomographyEmission tomography-computed tomographyTomography-computed tomographyIschemia-induced infarctionIschemic brainIschemic strokeStroke treatmentBrain penetrabilityBetulinic acidClinical managementEffective pharmacotherapyIntravenous administrationEffective treatmentMost therapeuticsEvaluation 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
2016
Synthesis 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 occupancy
2015
Brivaracetam, a selective high‐affinity synaptic vesicle protein 2A (SV2A) ligand with preclinical evidence of high brain permeability and fast onset of action
Nicolas JM, Hannestad J, Holden D, Kervyn S, Nabulsi N, Tytgat D, Huang Y, Chanteux H, Staelens L, Matagne A, Mathy FX, Mercier J, Stockis A, Carson RE, Klitgaard H. Brivaracetam, a selective high‐affinity synaptic vesicle protein 2A (SV2A) ligand with preclinical evidence of high brain permeability and fast onset of action. Epilepsia 2015, 57: 201-209. PMID: 26663401, DOI: 10.1111/epi.13267.Peer-Reviewed Original ResearchConceptsFaster onsetAcute seizuresHigh-affinity synaptic vesicle protein 2A ligandNonhuman primate PET studyAudiogenic seizure miceRapid brain entryOnset of actionSingle oral dosingHigh brain permeabilityBlood-brain barrier permeability (BBBP) valuesPrimate PET studyAudiogenic miceBrain entryCaco-2 cellsSeizure micePreclinical evidenceAntiepileptic drugsSusceptible miceBrain levelsBrain penetrationPreclinical dataBrain kineticsOral dosingSingle dosingClinical studies
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 purityEvaluation 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 Research