2022
Reversal of synapse loss in Alzheimer mouse models by targeting mGluR5 to prevent synaptic tagging by C1Q
Spurrier J, Nicholson L, Fang XT, Stoner AJ, Toyonaga T, Holden D, Siegert TR, Laird W, Allnutt MA, Chiasseu M, Brody AH, Takahashi H, Nies SH, Pérez-Cañamás A, Sadasivam P, Lee S, Li S, Zhang L, Huang YH, Carson RE, Cai Z, Strittmatter SM. Reversal of synapse loss in Alzheimer mouse models by targeting mGluR5 to prevent synaptic tagging by C1Q. Science Translational Medicine 2022, 14: eabi8593. PMID: 35648810, PMCID: PMC9554345, DOI: 10.1126/scitranslmed.abi8593.Peer-Reviewed Original ResearchConceptsPositron emission tomographySilent allosteric modulatorsAlzheimer's diseaseMouse modelPhospho-tau accumulationAged mouse modelAlzheimer mouse modelImmune-mediated attackSAM treatmentMicroglial mediatorsSynaptic engulfmentSynaptic lossAD miceComplement component C1qSynapse lossGlutamate responseSynaptic densityDrug washoutSynaptic localizationTherapeutic benefitCognitive impairmentAllosteric modulatorsEmission tomographyNonhuman primatesComponent C1q
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
2017
A 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 dose
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 loopChemotherapyMalignancy
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