2024
Deciphering the effects of radiopharmaceutical therapy in the tumor microenvironment of prostate cancer: an in-silico exploration with spatial transcriptomics
Hong J, Bae S, Cavinato L, Seifert R, Ryhiner M, Rominger A, Erlandsson K, Wilks M, Normandin M, El-Fakhri G, Choi H, Shi K. Deciphering the effects of radiopharmaceutical therapy in the tumor microenvironment of prostate cancer: an in-silico exploration with spatial transcriptomics. Theranostics 2024, 14: 7122-7139. DOI: 10.7150/thno.99516.Peer-Reviewed Original ResearchAssociation of T-cell subtypes with macrophage-specific arterial infiltration in people with HIV
Schnittman S, Talathi R, Wilks M, Hedgire S, Lu M, Fourman L, Alagpulinsa D, Stockman S, White K, Wallis Z, Autissier P, Stanley T, Lee H, Honigberg M, El-Fakhri G, Williams K, Zanni M, Grinspoon S, Toribio M. Association of T-cell subtypes with macrophage-specific arterial infiltration in people with HIV. AIDS 2024, 38: 1940-1946. PMID: 38905489, DOI: 10.1097/qad.0000000000003967.Peer-Reviewed Original ResearchArterial infiltrationCardiovascular diseaseIncreased risk of cardiovascular diseaseHuman immunodeficiency virusT cell subtypesT lymphocyte subpopulationsRisk of cardiovascular diseaseSystemic monocyte activationCardiovascular disease riskImmunodeficiency virusMonocyte activationHIV statusIncreased riskRelevant to atherogenesisHIVInfiltrationGeneral populationPWHEvidence of interactionSubtypesDiseaseSubpopulationsAtherogenesisRadiosynthesis automation, non-human primate biodistribution and dosimetry of K+ channel tracer [11C]3MeO4AP
Zhou Y, Wilks M, Dhaynaut M, Guehl N, Vesper D, Moon S, Rice P, El Fakhri G, Normandin M, Brugarolas P. Radiosynthesis automation, non-human primate biodistribution and dosimetry of K+ channel tracer [11C]3MeO4AP. EJNMMI Research 2024, 14: 43. PMID: 38683467, PMCID: PMC11058135, DOI: 10.1186/s13550-024-01092-8.Peer-Reviewed Original ResearchRadiation dosimetryAverage effective doseWhole-body biodistributionTotal scan timeNon-decayEffective doseNon-human primatesSymptomatic treatment of multiple sclerosisIn vivo binding affinityBed positionTreatment of multiple sclerosisHigh-resolution CTDynamic acquisition protocolDosimetryPET dataAdult rhesus macaquesScan timeImaging demyelinationOLINDA softwareRadiationAcquisition protocolsPreclinical studiesNo significant changesHigh dosesPET imaging
2023
Development and Pharmacochemical Characterization Discover a Novel Brain-Permeable HDAC11-Selective Inhibitor with Therapeutic Potential by Regulating Neuroinflammation in Mice
Bai P, Liu Y, Yang L, Ding W, Mondal P, Sang N, Liu G, Lu X, Ho T, Zhou Y, Wu R, Birar V, Wilks M, Tanzi R, Lin H, Zhang C, Li W, Shen S, Wang C. Development and Pharmacochemical Characterization Discover a Novel Brain-Permeable HDAC11-Selective Inhibitor with Therapeutic Potential by Regulating Neuroinflammation in Mice. Journal Of Medicinal Chemistry 2023, 66: 16075-16090. PMID: 37972387, DOI: 10.1021/acs.jmedchem.3c01491.Peer-Reviewed Original ResearchConceptsPositron emission tomographyNeuropathic painHDAC11 inhibitorsInhibition of HDAC11Histone deacetylase 11Pharmacokinetic/pharmacodynamic evaluationNeuroimmune functionMouse modelPharmacological inhibitionBrain uptakeEmission tomographyTherapeutic potentialNeurological indicationsPainTherapeutic targetHDAC11Regulating neuroinflammationNeurological disordersDrug developmentMiceInhibitorsHDAC isoformsCarbon-11Metabolic propertiesBrain
2022
Human biodistribution and radiation dosimetry of the demyelination tracer [18F]3F4AP
Brugarolas P, Wilks M, Noel J, Kaiser J, Vesper D, Ramos-Torres K, Guehl N, Macdonald-Soccorso M, Sun Y, Rice P, Yokell D, Lim R, Normandin M, El Fakhri G. Human biodistribution and radiation dosimetry of the demyelination tracer [18F]3F4AP. European Journal Of Nuclear Medicine And Molecular Imaging 2022, 50: 344-351. PMID: 36197499, PMCID: PMC9816249, DOI: 10.1007/s00259-022-05980-w.Peer-Reviewed Original ResearchConceptsRadiation dosimetryTime-activity curvesAdverse eventsEffective doseMultiple bed positionsComprehensive metabolic panelNonhuman primatesHealthy human volunteersNo adverse eventsDynamic PET scansVoltage-gated potassiumAnimal models of neurological diseasesNonhuman primate studiesModels of neurological diseasesHuman biodistributionAverage effective doseMetabolic panelDosimetryOLINDA softwareHealthy volunteersUrinary bladderPET scansDemyelinating lesionsBed positionAnimal modelsA positron emission tomography imaging probe selectively targeting the BD1 bromodomain and extra-terminal domain
Bai P, Yan L, Bagdasarian F, Wilks M, Wey H, Wang C. A positron emission tomography imaging probe selectively targeting the BD1 bromodomain and extra-terminal domain. Chemical Communications 2022, 58: 9654-9657. PMID: 35943085, PMCID: PMC9618257, DOI: 10.1039/d2cc03785h.Peer-Reviewed Original ResearchConceptsPositron emission tomography imaging studiesPositron emission tomographyNon-human primatesModerate brain uptakeImaging studiesBrain uptakePositron emission tomography imaging probeEmission tomographyBrain permeabilityBrainBromodomains of BRD2Clinical translationExtra-terminal domainTranslational potentialInhibitor developmentNeurological diseasesBinding specificityIncreased Macrophage-Specific Arterial Infiltration Relates to Noncalcified Plaque and Systemic Immune Activation in People With Human Immunodeficiency Virus
Toribio M, Wilks M, Hedgire S, Lu M, Cetlin M, Wang M, Alhallak I, Durbin C, White K, Wallis Z, Schnittman S, Stanley T, El-Fakhri G, Lee H, Autissier P, Zanni M, Williams K, Grinspoon S. Increased Macrophage-Specific Arterial Infiltration Relates to Noncalcified Plaque and Systemic Immune Activation in People With Human Immunodeficiency Virus. The Journal Of Infectious Diseases 2022, 226: 1823-1833. PMID: 35856671, PMCID: PMC10205602, DOI: 10.1093/infdis/jiac301.Peer-Reviewed Original ResearchConceptsHuman immunodeficiency virusAtherosclerotic cardiovascular diseaseAortic plaque volumeSystemic immune activationArterial infiltrationImmune activationImmunodeficiency virusPlaque volumeHistory of clinical ASCVDCD4+/CD8+ T-cell ratioHuman immunodeficiency virus statusCD8+ T cellsMarkers of immune activationClinical atherosclerotic cardiovascular diseasePersistent immune activationT cell ratioAtherosclerotic cardiovascular disease riskT cellsImmune phenotypeNoncalcified plaqueSystemic markersASCVD riskPWHCardiovascular diseaseUptake volume
2021
Near-Infrared Fluorescence Imaging of Carotid Plaques in an Atherosclerotic Murine Model
Wu X, Ulumben A, Long S, Katagiri W, Wilks M, Yuan H, Cortese B, Yang C, Kashiwagi S, Choi H, Normandin M, Fakhri G, Zaman R. Near-Infrared Fluorescence Imaging of Carotid Plaques in an Atherosclerotic Murine Model. Biomolecules 2021, 11: 1753. PMID: 34944397, PMCID: PMC8698491, DOI: 10.3390/biom11121753.Peer-Reviewed Original Research
2020
Positron annihilation localization by nanoscale magnetization
Gholami Y, Yuan H, Wilks M, Josephson L, El Fakhri G, Normandin M, Kuncic Z. Positron annihilation localization by nanoscale magnetization. Scientific Reports 2020, 10: 20262. PMID: 33219274, PMCID: PMC7680104, DOI: 10.1038/s41598-020-76980-9.Peer-Reviewed Original ResearchConceptsNanoscale magnetsSpatial resolution of PET imagesImproved dose localizationPositron emitting sourcesResolution of PET imagesPositron emission tomography instrumentationSpatial resolutionPositron emission tomographyAnnihilation quantaPhoton pairsPositron rangeDose localizationPositron annihilationCharged particlesOrtho-positroniumAnnihilationSuperparamagnetic iron oxide nanoparticlesCancer theranostic strategyPositron emission tomography scanPositronElectronic placesImage blurringPET imagingPET-MRITreatment outcomesEvaluation of the potassium channel tracer [18F]3F4AP in rhesus macaques
Guehl N, Ramos-Torres K, Linnman C, Moon S, Dhaynaut M, Wilks M, Han P, Ma C, Neelamegam R, Zhou Y, Popko B, Correia J, Reich D, Fakhri G, Herscovitch P, Normandin M, Brugarolas P. Evaluation of the potassium channel tracer [18F]3F4AP in rhesus macaques. Cerebrovascular And Brain Metabolism Reviews 2020, 41: 1721-1733. PMID: 33090071, PMCID: PMC8221756, DOI: 10.1177/0271678x20963404.Peer-Reviewed Original ResearchConceptsFocal brain injuryMyelin repair therapyContributions of demyelinationDrivers of disabilityImaging demyelinationBrain injuryMeasurements of molecular changesTool's sensitivity to changesLower myelin contentDemyelinating lesionsNeuronal conductionImpaired conductionDemyelinationBrain penetrationGold standardRhesus macaquesInjured areaMultiple sclerosisMolecular changesMyelin sheathNeurological diseasesHigh metabolic stabilityMRI methodsMRIInjuryA Radio-Nano-Platform for T1/T2 Dual-Mode PET-MR Imaging
Gholami Y, Yuan H, Wilks M, Maschmeyer R, Normandin M, Josephson L, Fakhri G, Kuncic Z. A Radio-Nano-Platform for T1/T2 Dual-Mode PET-MR Imaging. International Journal Of Nanomedicine 2020, 15: 1253-1266. PMID: 32161456, PMCID: PMC7049573, DOI: 10.2147/ijn.s241971.Peer-Reviewed Original ResearchConceptsLine spread functionPET-MR imagingSignal-to-noise ratioFull-width half-maximum (FWHMPET-MRHalf-maximum (FWHMSpatial resolutionTransmission electron microscopyImage quality gainSimultaneous positron emission tomographyContrast-enhanced diagnostic imagingAtom adsorptionPhantom imagesPositron emission tomographySpatial resolution of MRHybrid PET-MRRadio-isotopesSpread functionMulti-modal imaging techniquesSensitivity of positron emission tomographyMagnetic resonanceCo-registeredTransmission electron microscopy analysisSuper paramagnetic iron oxide nanoparticlesContrast agentsA Chelate-Free Nano-Platform for Incorporation of Diagnostic and Therapeutic Isotopes
Gholami Y, Josephson L, Akam E, Caravan P, Wilks M, Pan X, Maschmeyer R, Kolnick A, Fakhri G, Normandin M, Kuncic Z, Yuan H. A Chelate-Free Nano-Platform for Incorporation of Diagnostic and Therapeutic Isotopes. International Journal Of Nanomedicine 2020, 15: 31-47. PMID: 32021163, PMCID: PMC6954846, DOI: 10.2147/ijn.s227931.Peer-Reviewed Original ResearchConceptsDynamic light scatteringRadiochemical yieldSize exclusion chromatographyThin-layer chromatographyEmpty d orbitalsF-orbital electronsD-orbitalsICP-MSRelaxation spectrometryRadioactive isotopologuesMass spectrometryInductively coupled plasma mass spectrometryChelate-freeNonradioactive metalsPositive chargePlasma mass spectrometryFh NPsNanoparticlesReaction timeLight scatteringMetalExclusion chromatographySpectrometryApproved drugsReaction
2019
Assessing the interactions between radiotherapy and antitumour immunity
Grassberger C, Ellsworth S, Wilks M, Keane F, Loeffler J. Assessing the interactions between radiotherapy and antitumour immunity. Nature Reviews Clinical Oncology 2019, 16: 729-745. PMID: 31243334, DOI: 10.1038/s41571-019-0238-9.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsCheckpoint inhibitorsIntroduction of immune checkpoint inhibitorsTherapy-induced immune responsesLong-term tumor controlImmune responsePre-existing immune responsesImmune response to radiotherapyInteraction of immunotherapyResponse to radiotherapyAdvanced-stage diseaseRadiation-induced immunosuppressionImmune cell dynamicsSite of diseaseIndividualized treatment approachPatient levelAntitumour immunityRadiotherapy regimensTumor controlTreatment of cancerIncrease response ratesRadiotherapyImmunotherapySerum biomarkersClinical data
2018
Development and Application of FASA, a Model for Quantifying Fatty Acid Metabolism Using Stable Isotope Labeling
Argus J, Wilks M, Zhou Q, Hsieh W, Khialeeva E, Hoi X, Bui V, Xu S, Yu A, Wang E, Herschman H, Williams K, Bensinger S. Development and Application of FASA, a Model for Quantifying Fatty Acid Metabolism Using Stable Isotope Labeling. Cell Reports 2018, 25: 2919-2934.e8. PMID: 30517876, PMCID: PMC6432944, DOI: 10.1016/j.celrep.2018.11.041.Peer-Reviewed Original ResearchConceptsFatty acid metabolismHomeostasis of fatty acidsCellular fatty acid contentCellular fatty acid metabolismAcid metabolismMovement of fatty acidsPolyunsaturated fatty acid poolStable isotope labelingFatty acidsFatty acid homeostasisElongation pathwayFatty acid poolAcid homeostasisMetabolic stepsContribution of synthesisAcid poolPro-inflammatory stimuliFatty acid contentIsotope labelingInflammatory signalingAcid contentMetabolismCellsElongationAcidHeat-induced radiolabeling and fluorescence labeling of Feraheme nanoparticles for PET/SPECT imaging and flow cytometry
Yuan H, Wilks M, Normandin M, El Fakhri G, Kaittanis C, Josephson L. Heat-induced radiolabeling and fluorescence labeling of Feraheme nanoparticles for PET/SPECT imaging and flow cytometry. Nature Protocols 2018, 13: 392-412. PMID: 29370158, PMCID: PMC5966297, DOI: 10.1038/nprot.2017.133.Peer-Reviewed Original Research
2017
Mature B cells accelerate wound healing after acute and chronic diabetic skin lesions
Sîrbulescu R, Boehm C, Soon E, Wilks M, Ilieş I, Yuan H, Maxner B, Chronos N, Kaittanis C, Normandin M, Fakhri G, Orgill D, Sluder A, Poznansky M. Mature B cells accelerate wound healing after acute and chronic diabetic skin lesions. Wound Repair And Regeneration 2017, 25: 774-791. PMID: 28922523, PMCID: PMC5760362, DOI: 10.1111/wrr.12584.Peer-Reviewed Original ResearchConceptsB cell treatmentB cellsKinetics of neutrophil infiltrationImmune cell populationsNaive B cellsWild-type miceSaline-treated controlsMature B cellsGrowth-associated protein 43Wound healingIncreased collagen depositionDiabetic murine woundsObese diabetic micePro-healing responseIncreased fibroblast proliferationWound granulation tissueT cellsIncreased relative expressionNeutrophil infiltrationLive B cellsScar sizeDiabetic miceDecreased apoptosisTopical applicationMMP2 expressionHeat-induced-radiolabeling and click chemistry: A powerful combination for generating multifunctional nanomaterials
Yuan H, Wilks M, Fakhri G, Normandin M, Kaittanis C, Josephson L. Heat-induced-radiolabeling and click chemistry: A powerful combination for generating multifunctional nanomaterials. PLOS ONE 2017, 12: e0172722. PMID: 28225818, PMCID: PMC5321420, DOI: 10.1371/journal.pone.0172722.Peer-Reviewed Original ResearchConceptsClick reactionClick chemistryCopper-free click reactionCopper-catalyzedAzide groupsBiomolecule attachmentReporter groupNP surfaceTargeted nanoparticlesNanoparticlesBioactive groupsMultifunctional nanomaterialsBiomedical applicationsSynthesisIntermediateReactionChemistryNanomaterialsBiomoleculesAlkynesCombination of techniquesCell surface receptorsAzideTherapeutic agentsClickApplication of a Novel CD206+ Macrophage-Specific Arterial Imaging Strategy in HIV-Infected Individuals
Zanni M, Toribio M, Wilks M, Lu M, Burdo T, Walker J, Autissier P, Foldyna B, Stone L, Martin A, Cope F, Abbruzzese B, Brady T, Hoffmann U, Williams K, El-Fakhri G, Grinspoon S. Application of a Novel CD206+ Macrophage-Specific Arterial Imaging Strategy in HIV-Infected Individuals. The Journal Of Infectious Diseases 2017, 215: 1264-1269. PMID: 28204544, PMCID: PMC5853590, DOI: 10.1093/infdis/jix095.Peer-Reviewed Original ResearchMeSH KeywordsAortaAtherosclerosisCase-Control StudiesCross-Sectional StudiesDextransHIV InfectionsHumansLectins, C-TypeLymph NodesMacrophagesMaleMannansMannose ReceptorMannose-Binding LectinsMiddle AgedPlaque, AtheroscleroticRadiopharmaceuticalsReceptors, Cell SurfaceRegression AnalysisSingle Photon Emission Computed Tomography Computed TomographyTechnetium Tc 99m PentetateUnited StatesConceptsSingle-photon emission computed tomography/computed tomographyFirst-in-human dataNon-HIV-infected subjectsAortic plaque volumeHIV-infected subjectsHIV-infected individualsMacrophages ex vivoComputed tomographic angiographyCD206+ macrophagesTomography/computed tomographyTomographic angiographyImaging techniquesTechnetium TcHIV statusPlaque volumeCardiovascular diseaseHIVImaging strategiesCD206In vivo applicationsSubjectsTilmanoceptAngiographyMacrophagesTomography
2015
Limiting Cholesterol Biosynthetic Flux Spontaneously Engages Type I IFN Signaling
York AG, Williams KJ, Argus JP, Zhou QD, Brar G, Vergnes L, Gray EE, Zhen A, Wu NC, Yamada DH, Cunningham CR, Tarling EJ, Wilks MQ, Casero D, Gray DH, Yu AK, Wang ES, Brooks DG, Sun R, Kitchen SG, Wu TT, Reue K, Stetson DB, Bensinger SJ. Limiting Cholesterol Biosynthetic Flux Spontaneously Engages Type I IFN Signaling. Cell 2015, 163: 1716-1729. PMID: 26686653, PMCID: PMC4783382, DOI: 10.1016/j.cell.2015.11.045.Peer-Reviewed Original ResearchConceptsImport of cholesterolI interferonType I IFNsSTING-dependent mannerCholesterol biosynthetic pathwayI IFNsCombination of biosynthesisBiosynthetic fluxBiosynthetic pathwayLong-chain fatty acidsIsotope tracer analysisMetabolic shiftMetabolic pathwaysType I interferonCholesterol biosynthesisLipid requirementsChain fatty acidsInnate immunityBiosynthesisFatty acidsPool sizePathwayMechanistic studiesViral challengeFree cholesterolHeat‐Induced Radiolabeling of Nanoparticles for Monocyte Tracking by PET
Normandin M, Yuan H, Wilks M, Chen H, Kinsella J, Cho H, Guehl N, Absi‐Halabi N, Hosseini S, Fakhri G, Sosnovik D, Josephson L. Heat‐Induced Radiolabeling of Nanoparticles for Monocyte Tracking by PET. Angewandte Chemie 2015, 127: 13194-13198. DOI: 10.1002/ange.201505525.Peer-Reviewed Original ResearchPositron emission tomographyRadiolabelling of nanoparticlesStandardized uptake valueMonocytes in vitroNP pharmacokineticsSlow uptake processUptake valueLymph nodesCirculating monocytesMonocyte traffickingIV injectionImmune responseBlood clearanceEmission tomographyHepatic uptakeMonocytesPharmacokineticsLymphUptake process