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 imagingPreclinical 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 trialsIn vivo imaging of cerebral glucose metabolism informs on subacute to chronic post-stroke tissue status – A pilot study combining PET and deuterium metabolic imaging
Meerwaldt A, Straathof M, Oosterveld W, van Heijningen C, van Leent M, Toner Y, Munitz J, Teunissen A, Daemen C, van der Toorn A, van Vliet G, van Tilborg G, De Feyter H, de Graaf R, Hol E, Mulder W, Dijkhuizen R. In vivo imaging of cerebral glucose metabolism informs on subacute to chronic post-stroke tissue status – A pilot study combining PET and deuterium metabolic imaging. Cerebrovascular And Brain Metabolism Reviews 2023, 43: 778-790. PMID: 36606595, PMCID: PMC10108187, DOI: 10.1177/0271678x221148970.Peer-Reviewed Original ResearchConceptsTransient middle cerebral artery occlusionPositron emission tomographyGlucose metabolismPost-ischemic brain tissueMiddle cerebral artery occlusionFDG positron emission tomographyFluorodeoxyglucose positron emission tomographyMetabolic imagingSignificant glial activationAcute ischemic strokeCerebral artery occlusionCerebral energy metabolismDeuterium metabolic imagingActive glucose metabolismGlial activationRecanalization therapyArtery occlusionIschemic strokeStroke severityCerebral perfusionC57BL/6 micePoor outcomeElevated lactate productionPathophysiological changesBaseline values
2021
NMR visibility of deuterium‐labeled liver glycogen in vivo
De Feyter HM, Thomas MA, Behar KL, de Graaf R. NMR visibility of deuterium‐labeled liver glycogen in vivo. Magnetic Resonance In Medicine 2021, 86: 62-68. PMID: 33590529, PMCID: PMC8005460, DOI: 10.1002/mrm.28717.Peer-Reviewed Original Research
2020
Characterization of Kinetic Isotope Effects and Label Loss in Deuterium-Based Isotopic Labeling Studies
de Graaf RA, Thomas MA, Behar KL, De Feyter HM. Characterization of Kinetic Isotope Effects and Label Loss in Deuterium-Based Isotopic Labeling Studies. ACS Chemical Neuroscience 2020, 12: 234-243. PMID: 33319987, PMCID: PMC9890388, DOI: 10.1021/acschemneuro.0c00711.Peer-Reviewed Original Research
2019
On the magnetic field dependence of deuterium metabolic imaging
de Graaf R, Hendriks AD, Klomp DWJ, Kumaragamage C, Welting D, de Castro C, Brown PB, McIntyre S, Nixon TW, Prompers JJ, De Feyter HM. On the magnetic field dependence of deuterium metabolic imaging. NMR In Biomedicine 2019, 33: e4235. PMID: 31879985, PMCID: PMC7141779, DOI: 10.1002/nbm.4235.Peer-Reviewed Original ResearchIn vivo 13C and 1H‐[13C] MRS studies of neuroenergetics and neurotransmitter cycling, applications to neurological and psychiatric disease and brain cancer
Rothman DL, de Graaf R, Hyder F, Mason GF, Behar KL, De Feyter HM. In vivo 13C and 1H‐[13C] MRS studies of neuroenergetics and neurotransmitter cycling, applications to neurological and psychiatric disease and brain cancer. NMR In Biomedicine 2019, 32: e4172. PMID: 31478594, DOI: 10.1002/nbm.4172.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
2018
Deuterium metabolic imaging (DMI) for MRI-based 3D mapping of metabolism in vivo
De Feyter HM, Behar KL, Corbin ZA, Fulbright RK, Brown PB, McIntyre S, Nixon TW, Rothman DL, de Graaf RA. Deuterium metabolic imaging (DMI) for MRI-based 3D mapping of metabolism in vivo. Science Advances 2018, 4: eaat7314. PMID: 30140744, PMCID: PMC6105304, DOI: 10.1126/sciadv.aat7314.Peer-Reviewed Original ResearchConceptsOral intakeMetabolic imagingGlucose uptakeHigh-grade brain tumorsRat glioma modelPositron emission tomography (PET) detectionSimilar metabolic patternMetabolic imaging techniquesDeuterium metabolic imagingHigher glucose uptakeGlucose analog 2FDG-PETF-fluoroIntravenous infusionBrain tumorsGlioma modelGlucose metabolismNormal brainTomography detectionAnimal modelsMagnetic resonance spectroscopicTumor tissueHuman liverMetabolic patternsNoninvasive approach
2017
In vivo proton observed carbon edited (POCE) 13C magnetic resonance spectroscopy of the rat brain using a volumetric transmitter and receive‐only surface coil on the proton channel
Kumaragamage C, Madularu D, Mathieu AP, De Feyter H, Rajah MN, Near J. In vivo proton observed carbon edited (POCE) 13C magnetic resonance spectroscopy of the rat brain using a volumetric transmitter and receive‐only surface coil on the proton channel. Magnetic Resonance In Medicine 2017, 79: 628-635. PMID: 28497464, DOI: 10.1002/mrm.26751.Peer-Reviewed Original Research2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity
Sulkowski PL, Corso CD, Robinson ND, Scanlon SE, Purshouse KR, Bai H, Liu Y, Sundaram RK, Hegan DC, Fons NR, Breuer GA, Song Y, Mishra-Gorur K, De Feyter HM, de Graaf RA, Surovtseva YV, Kachman M, Halene S, Günel M, Glazer PM, Bindra RS. 2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity. Science Translational Medicine 2017, 9 PMID: 28148839, PMCID: PMC5435119, DOI: 10.1126/scitranslmed.aal2463.Peer-Reviewed Original ResearchConceptsIsocitrate dehydrogenase 1PARP inhibitor sensitivityPossible therapeutic strategiesHomologous recombination defectsTherapeutic strategiesTumor xenograftsInhibitor sensitivityPathologic processesSmall molecule inhibitorsIDH1/2 mutationsTumor progressionIDH2 mutationsMutant IDHPolymerase inhibitorsGlioma cellsTumor cellsHR deficiencyPARP inhibitionIDH mutationsInhibitory effectDehydrogenase 1Neomorphic activityMutant IDH1 enzymeDependent dioxygenasesMutant cells
2016
A ketogenic diet increases transport and oxidation of ketone bodies in RG2 and 9L gliomas without affecting tumor growth
De Feyter HM, Behar KL, Rao JU, Madden-Hennessey K, Ip KL, Hyder F, Drewes LR, Geschwind JF, de Graaf RA, Rothman DL. A ketogenic diet increases transport and oxidation of ketone bodies in RG2 and 9L gliomas without affecting tumor growth. Neuro-Oncology 2016, 18: 1079-1087. PMID: 27142056, PMCID: PMC4933488, DOI: 10.1093/neuonc/now088.Peer-Reviewed Original ResearchConceptsKetone body oxidationKetogenic dietKetone bodiesGlioma modelBrain tumorsBrain tumor metabolismCortical brain tissuePlasma glucose concentrationRat glioma modelRodent glioma modelsContralateral brainRat gliomaTumor growthBrain tissueTumor metabolismBeta-hydroxybutyrate oxidationTumor cellsGliomasMR spectroscopyTumor's abilityMonocarboxylate transportersDietGlucose concentrationKetone body transportTherapy
2011
13C MRS studies of neuroenergetics and neurotransmitter cycling in humans
Rothman DL, De Feyter HM, de Graaf R, Mason GF, Behar KL. 13C MRS studies of neuroenergetics and neurotransmitter cycling in humans. NMR In Biomedicine 2011, 24: 943-957. PMID: 21882281, PMCID: PMC3651027, DOI: 10.1002/nbm.1772.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsNeurotransmitter cyclingMRS studiesHigh neuronal activityHuman brain diseasesOnly noninvasive methodBrain metabolismGlutamate neurotransmissionNeuronal activityPsychiatric diseasesNeuronal functionBrain diseasesBrain functionClinical researchNeuroenergeticsNoninvasive methodMRSMRS measurementsHuman researchDiseaseBrain statesRecent findingsImportant new informationHumansMetabolic pathwaysNeurotransmission
2010
Adaptations in Mitochondrial Function Parallel, but Fail to Rescue, the Transition to Severe Hyperglycemia and Hyperinsulinemia: A Study in Zucker Diabetic Fatty Rats
Lenaers E, De Feyter H, Hoeks J, Schrauwen P, Schaart G, Nabben M, Nicolay K, Prompers J, Hesselink M. Adaptations in Mitochondrial Function Parallel, but Fail to Rescue, the Transition to Severe Hyperglycemia and Hyperinsulinemia: A Study in Zucker Diabetic Fatty Rats. Obesity 2010, 18: 1100-1107. PMID: 19875988, DOI: 10.1038/oby.2009.372.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalAdenine Nucleotide Translocator 1AnimalsDiabetes Mellitus, ExperimentalHyperglycemiaHyperinsulinismIon ChannelsMaleMitochondria, MuscleMitochondrial ProteinsMuscle Fibers, SkeletalObesityOxidation-ReductionOxygen ConsumptionProtein CarbonylationRatsRats, ZuckerSeverity of Illness IndexUncoupling Protein 3ConceptsUncoupling protein 3Palmitoyl-CoAMitochondrial functionZucker diabetic fattyFat oxidative capacityReduced fat oxidative capacityProgressive development of insulin resistanceMitochondrial defectsDevelopment of insulin resistanceCarbonyl cyanide p-trifluoromethoxyphenylhydrazoneIntrinsic mitochondrial defectIntrinsic mitochondrial functionInsulin resistanceMitochondrial dysfunctionMuscle mitochondrial functionPyruvate oxidationMitochondrial adaptationsType 2 diabetesState 3Development of type 2 diabetesMitochondrial capacityProtein 3Fa/fa ratsP-trifluoromethoxyphenylhydrazonePyruvate