2023
Intrathecal delivery of nanoparticle PARP inhibitor to the cerebrospinal fluid for the treatment of metastatic medulloblastoma
Khang M, Lee J, Lee T, Suh H, Lee S, Cavaliere A, Rushing A, Geraldo L, Belitzky E, Rossano S, de Feyter H, Shin K, Huttner A, Roussel M, Thomas J, Carson R, Marquez-Nostra B, Bindra R, Saltzman W. Intrathecal delivery of nanoparticle PARP inhibitor to the cerebrospinal fluid for the treatment of metastatic medulloblastoma. Science Translational Medicine 2023, 15: eadi1617. PMID: 37910601, PMCID: PMC11078331, DOI: 10.1126/scitranslmed.adi1617.Peer-Reviewed Original ResearchConceptsCerebrospinal fluidDelivery of drugsEffective therapyTherapeutic indexPARP inhibitorsBlood-brain barrierSite of tumorRapid systemic clearanceXenograft mouse modelSolvent evaporation processAdministration of substancesLeptomeningeal spreadIntrathecal deliveryLeptomeningeal metastasesBrain penetrationSystemic clearanceTumor regressionPolymer nanoparticlesMetastatic medulloblastomaMouse modelPediatric medulloblastomaDrug accumulationCSF turnoverEncapsulated drugsPET imagingDecreased synaptic vesicle glycoprotein 2A binding in a rodent model of familial Alzheimer's disease detected by [18F]SDM-16
Zheng C, Toyonaga T, Chen B, Nicholson L, Mennie W, Liu M, Spurrier J, Deluca K, Strittmatter S, Carson R, Huang Y, Cai Z. Decreased synaptic vesicle glycoprotein 2A binding in a rodent model of familial Alzheimer's disease detected by [18F]SDM-16. Frontiers In Neurology 2023, 14: 1045644. PMID: 36846134, PMCID: PMC9945093, DOI: 10.3389/fneur.2023.1045644.Peer-Reviewed Original ResearchStandardized uptake value ratioDistribution volume ratioAlzheimer's diseaseSimplified reference tissue modelSynapse lossMouse modelAPP/PS1 miceAge-matched wild-type miceAPPswe/PS1dE9 mouse modelAPP/PS1 AD mouse modelSlow brain kineticsAD mouse modelSynaptic vesicle glycoprotein 2APseudo-reference regionWild-type miceUptake value ratioMonths of ageDifferent brain regionsDifferent imaging windowsFamilial Alzheimer's diseasePET imaging studiesReference tissue modelPS1 miceBrain stemBrain kinetics
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
2020
Quantification of SV2A Binding in Rodent Brain Using [18F]SynVesT-1 and PET Imaging
Sadasivam P, Fang XT, Toyonaga T, Lee S, Xu Y, Zheng MQ, Spurrier J, Huang Y, Strittmatter SM, Carson RE, Cai Z. Quantification of SV2A Binding in Rodent Brain Using [18F]SynVesT-1 and PET Imaging. Molecular Imaging And Biology 2020, 23: 372-381. PMID: 33258040, PMCID: PMC8105262, DOI: 10.1007/s11307-020-01567-9.Peer-Reviewed Original ResearchConceptsBrain stemAlzheimer's diseaseMin postinjectionAnimal modelsAPP/PS1 miceReference regionStandardized uptake value ratioDynamic PET imaging dataUptake value ratioRodent brain tissueStatic PET scansDifferent imaging windowsPET imaging dataWild-type controlsReference tissue modelPS1 miceAD pathogenesisTherapeutic effectMouse modelRodent modelsLittermate controlsPET scansRodent brainPreclinical imaging studiesTherapeutic drug efficacy