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 imaging
2022
Deuterium metabolic imaging of the human brain in vivo at 7 T
Roig E, De Feyter HM, Nixon TW, Ruhm L, Nikulin AV, Scheffler K, Avdievich NI, Henning A, de Graaf R. Deuterium metabolic imaging of the human brain in vivo at 7 T. Magnetic Resonance In Medicine 2022, 89: 29-39. PMID: 36063499, PMCID: PMC9756916, DOI: 10.1002/mrm.29439.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
Selective proton‐observed, carbon‐edited (selPOCE) MRS method for measurement of glutamate and glutamine 13C‐labeling in the human frontal cortex
De Feyter H, Herzog RI, Steensma BR, Klomp DWJ, Brown PB, Mason GF, Rothman DL, de Graaf R. Selective proton‐observed, carbon‐edited (selPOCE) MRS method for measurement of glutamate and glutamine 13C‐labeling in the human frontal cortex. Magnetic Resonance In Medicine 2017, 80: 11-20. PMID: 29134686, PMCID: PMC5876108, DOI: 10.1002/mrm.27003.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
Detection of cerebral NAD+ in humans at 7T
de Graaf R, De Feyter H, Brown PB, Nixon TW, Rothman DL, Behar KL. Detection of cerebral NAD+ in humans at 7T. Magnetic Resonance In Medicine 2016, 78: 828-835. PMID: 27670385, PMCID: PMC5366282, DOI: 10.1002/mrm.26465.Peer-Reviewed Original Research
2013
Increased Brain Lactate Concentrations Without Increased Lactate Oxidation During Hypoglycemia in Type 1 Diabetic Individuals
De Feyter HM, Mason GF, Shulman GI, Rothman DL, Petersen KF. Increased Brain Lactate Concentrations Without Increased Lactate Oxidation During Hypoglycemia in Type 1 Diabetic Individuals. Diabetes 2013, 62: 3075-3080. PMID: 23715622, PMCID: PMC3749358, DOI: 10.2337/db13-0313.Peer-Reviewed Original ResearchConceptsBrain lactate concentrationBlood-brain barrierHypoglycemia unawarenessLactate concentrationT1D subjectsControl subjectsType 1 diabetic subjectsType 1 diabetic individualsBlood-borne lactateNondiabetic control subjectsPlasma lactate concentrationMonocarboxylic acid transportDiabetic subjectsHypoglycemic clampT1D patientsDiabetic individualsBrain metabolismBrain fuelBrain glutamateBrain energeticsHypoglycemiaPatientsMetabolic adaptationAcid transportSubjectsIncreased Brain Transport and Metabolism of Acetate in Hypoglycemia Unawareness
Gulanski BI, De Feyter HM, Page KA, Belfort-DeAguiar R, Mason GF, Rothman DL, Sherwin RS. Increased Brain Transport and Metabolism of Acetate in Hypoglycemia Unawareness. The Journal Of Clinical Endocrinology & Metabolism 2013, 98: 3811-3820. PMID: 23796565, PMCID: PMC4425818, DOI: 10.1210/jc.2013-1701.Peer-Reviewed Original ResearchConceptsHypoglycemia-associated autonomic failureHypoglycemia unawarenessT1DM individualsEpinephrine levelsBrain transportControl groupType 1 diabetes mellitusDefective glucose counterregulationHealthy nondiabetic controlsSevere hypoglycemia unawarenessIntensive insulin therapyLong-term complicationsHospital research unitEntire study populationT1DM participantsAutonomic failureGlucose counterregulationInsulin therapyDiabetes mellitusNondiabetic controlsCerebral cortexAcute hypoglycemiaT1DM controlsCerebral energeticsStudy population
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