2022
Impact of 40 Hz Transcranial Alternating Current Stimulation on Cerebral Tau Burden in Patients with Alzheimer’s Disease: A Case Series1
Dhaynaut M, Sprugnoli G, Cappon D, Macone J, Sanchez J, Normandin M, Guehl N, Koch G, Paciorek R, Connor A, Press D, Johnson K, Pascual-Leone A, Fakhri G, Santarnecchi E. Impact of 40 Hz Transcranial Alternating Current Stimulation on Cerebral Tau Burden in Patients with Alzheimer’s Disease: A Case Series1. Journal Of Alzheimer's Disease 2022, 85: 1667-1676. PMID: 34958021, PMCID: PMC9023125, DOI: 10.3233/jad-215072.Peer-Reviewed Original ResearchConceptsMicroglia activationGamma spectral powerDecrease of microglia activationNo adverse eventsTranscranial alternating current stimulationSlow disease progressionPlacebo-controlled conditionsPreclinical dataCase seriesAdverse eventsGamma oscillationsElectrophysiological assessmentP-tauMouse modelDisease progressionMesial regionMild to moderate ADAnimal modelsPatientsPET imagingAlzheimer's diseaseSpectral powerAD mouse modelAD patientsProtein clearance
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 ResearchEvaluation of Fluorinated Cromolyn Derivatives as Potential Therapeutics for Alzheimer’s Disease
Shoup T, Griciuc A, Normandin M, Quinti L, Walsh L, Dhaynaut M, Moon S, Guehl N, Brugarolas P, Elmaleh D, Fakhri G, Tanzi R. Evaluation of Fluorinated Cromolyn Derivatives as Potential Therapeutics for Alzheimer’s Disease. Journal Of Alzheimer's Disease 2021, 80: 775-786. PMID: 33579853, DOI: 10.3233/jad-201419.Peer-Reviewed Original ResearchConceptsMicroglial cellsCell toxicityPET imagingMultifactorial mechanism of actionBV2 microglial cellsDose-dependent mannerBV2 microglial cell lineMicroglial cell lineMechanism of actionF-18Multifactorial mechanismsPro-inflammatoryHigher perfusionLow perfusionRhesus macaquesCromolynCell linesIncreased uptakeTracer penetrationEnhanced uptakePotential therapeuticsPerfusionToxicityClearance assayClearanceSynthesis and Characterization of [18F]JNJ-46356479 as the First 18F-Labeled PET Imaging Ligand for Metabotropic Glutamate Receptor 2
Yuan G, Guehl N, Zheng B, Qu X, Moon S, Dhaynaut M, Shoup T, Afshar S, Kang H, Zhang Z, El Fakhri G, Normandin M, Brownell A. Synthesis and Characterization of [18F]JNJ-46356479 as the First 18F-Labeled PET Imaging Ligand for Metabotropic Glutamate Receptor 2. Molecular Imaging And Biology 2021, 23: 527-536. PMID: 33559035, PMCID: PMC8277681, DOI: 10.1007/s11307-021-01586-0.Peer-Reviewed Original ResearchConceptsNon-human primatesIn vivo PET imaging studiesNucleus accumbensGlutamate receptor 2PET imaging ligandsImaging ligandsParietal cortexBrain regionsPET imaging studiesPET radioligandIn vivo PET imaging experimentsVolume of distributionMGluR2C57BL/6 J micePET imaging experimentsPET studiesBrainSprague-Dawley ratsAlzheimer's diseaseBrain permeabilityPre-treatment studyImaging studiesDisordersRat studiesReversible kinetics
2020
Design, Synthesis, and Characterization of Benzimidazole Derivatives as Positron Emission Tomography Imaging Ligands for Metabotropic Glutamate Receptor 2
Yuan G, Qu X, Zheng B, Neelamegam R, Afshar S, Iyengar S, Pan C, Wang J, Kang H, Ondrechen M, Poutiainen P, Fakhri G, Zhang Z, Brownell A. Design, Synthesis, and Characterization of Benzimidazole Derivatives as Positron Emission Tomography Imaging Ligands for Metabotropic Glutamate Receptor 2. Journal Of Medicinal Chemistry 2020, 63: 12060-12072. PMID: 32981322, PMCID: PMC8629109, DOI: 10.1021/acs.jmedchem.0c01394.Peer-Reviewed Original ResearchConceptsPotential positron emission tomographyBenzimidazole derivativesPositron emission tomography imaging ligandsExcellent selectivityImaging ligandsPositive allosteric modulatorsRadiochemical yieldBinding affinityMetabotropic glutamate receptor 2C]methyl iodideMolar activityLigandDerivativesRadiochemical purityGlutamate receptor 2Brain regionsAllosteric modulatorsPositron emission tomographyC]methylationRadiochemicalIodideBrain uptakeMGluR subtypesCompoundsBindingNon-Invasive Photoacoustic Imaging of In Vivo Mice with Erythrocyte Derived Optical Nanoparticles to Detect CAD/MI
Liu Y, Hanley T, Chen H, Long S, Gambhir S, Cheng Z, Wu J, Fakhri G, Anvari B, Zaman R. Non-Invasive Photoacoustic Imaging of In Vivo Mice with Erythrocyte Derived Optical Nanoparticles to Detect CAD/MI. Scientific Reports 2020, 10: 5983. PMID: 32249814, PMCID: PMC7136251, DOI: 10.1038/s41598-020-62868-1.Peer-Reviewed Original ResearchConceptsCoronary artery diseaseMyocardial-infarctionTail vein 1 hourIndocyanine greenWeeks old male C57BL/6 miceLeft anterior descending (LADAnterior descending (LADMale C57BL/6 miceAtherosclerotic lesionsCoronary artery ligationTen-week-old male C57BL/6 miceAtherosclerotic plaquesC57BL/6 miceNon-invasiveArtery ligationInflammatory cellsPortal tractsArtery diseaseFluorescence in vivo imagingParenchymal necrosisCoronary arteryClinical detectionPathological changesContrast agentsLesions
2019
Renal clearable nanochelators for iron overload therapy
Kang H, Han M, Xue J, Baek Y, Chang J, Hu S, Nam H, Jo M, El Fakhri G, Hutchens M, Choi H, Kim J. Renal clearable nanochelators for iron overload therapy. Nature Communications 2019, 10: 5134. PMID: 31723130, PMCID: PMC6853917, DOI: 10.1038/s41467-019-13143-z.Peer-Reviewed Original ResearchConceptsIron overloadIntravenous injectionDaily sc injectionsUrinary iron excretionSecondary iron overloadIron-overloaded miceAdverse side effectsIron chelatorsIron overload disordersGastrointestinal bleedingSC injectionIron excretionLiver fibrosisSide effectsKidney damageKidney failureIron overload therapyIron levelsToxic ironPharmacokinetic propertiesDeferoxamineNanochelatorKidneyExcretionInjectionReal‐Time Imaging of Vaccine Biodistribution Using Zwitterionic NIR Nanoparticles
Katagiri W, Lee J, Tétrault M, Kang H, Jeong S, Evans C, Yokomizo S, Santos S, Jones C, Hu S, Fakhri G, Tsukada K, Choi H, Kashiwagi S. Real‐Time Imaging of Vaccine Biodistribution Using Zwitterionic NIR Nanoparticles. Advanced Healthcare Materials 2019, 8: e1900035. PMID: 31165556, PMCID: PMC6687515, DOI: 10.1002/adhm.201900035.Peer-Reviewed Original ResearchConceptsNIR fluorescence imaging systemLymph nodesVaccine antigensClinical vaccine candidatesOptimization of vaccine designFluorescence imaging systemAntigen presenting cellsInduce protective immune responsesSecondary lymphoid tissuesDelivery of vaccine antigensProtective immune responsesZwitterionic NIR fluorophoreFlow cytometry analysisPresenting cellsLymphoid tissueIntradermal administrationAdverse reactionsBioconjugate vaccineImmune responseVaccine designVaccine candidatesModel vaccineCytometry analysisZwitterionic fluorophoresAntigenLysosome‐Targeted Bioprobes for Sequential Cell Tracking from Macroscopic to Microscopic Scales
Park G, Lee J, Levitz A, Fakhri G, Hwang N, Henary M, Choi H. Lysosome‐Targeted Bioprobes for Sequential Cell Tracking from Macroscopic to Microscopic Scales. Advanced Materials 2019, 31: e1806216. PMID: 30740778, PMCID: PMC6574216, DOI: 10.1002/adma.201806216.Peer-Reviewed Original ResearchConceptsMechanism of actionEfficient cellular labellingLive cell trackingCytoplasmic membraneCell trackingOptical propertiesLiving cellsNear-infraredCell-based therapeuticsHost tissuesTrackingCellular analysisLipophilic cationsChemical treatmentCellular effluxLiving organismsTarget cellsCellsCellular retentionExcellent cell permeationTarget tissues
2018
[18F]Fluorocholine and [18F]Fluoroacetate PET as Imaging Biomarkers to Assess Phosphatidylcholine and Mitochondrial Metabolism in Preclinical Models of TSC and LAM
Verwer E, Kavanagh T, Mischler W, Feng Y, Takahashi K, Wang S, Shoup T, Neelamegam R, Yang J, Guehl N, Ran C, Massefski W, Cui Y, El-Chemaly S, Sadow P, Oldham W, Kijewski M, Fakhri G, Normandin M, Priolo C. [18F]Fluorocholine and [18F]Fluoroacetate PET as Imaging Biomarkers to Assess Phosphatidylcholine and Mitochondrial Metabolism in Preclinical Models of TSC and LAM. Clinical Cancer Research 2018, 24: 5925-5938. PMID: 30054282, PMCID: PMC6816044, DOI: 10.1158/1078-0432.ccr-17-3693.Peer-Reviewed Original ResearchMeSH KeywordsAgedAnimalsBiomarkersCholineDisease Models, AnimalFemaleFluoroacetatesHeterograftsHumansImage Processing, Computer-AssistedImmunohistochemistryLipid MetabolismLymphangioleiomyomatosisMaleMiceMice, TransgenicMitochondriaOxygen ConsumptionPhosphatidylcholinesPositron-Emission TomographyRatsTuberous SclerosisConceptsTuberous sclerosis complexMetabolic imaging biomarkersPreclinical modelsImaging biomarkersTSC2-deficient cellsStandardized uptake valueTuberous sclerosis complex manifestationsModels of tuberous sclerosis complexAutosomal dominant disorderPotential clinical interestBenign tumorsOvariectomized miceUptake valueSubcutaneous tumorsPreclinical studiesPulmonary nodulesCystic destructionLymphangioleiomyomatosisDominant disorderProliferative lesionsInactivating mutationsTumorMetabolic reprogrammingNeurocognitive impairmentPET imaging
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 expressionSynthesis and preliminary PET imaging of 11C and 18F isotopologues of the ROS1/ALK inhibitor lorlatinib
Collier T, Normandin M, Stephenson N, Livni E, Liang S, Wooten D, Esfahani S, Stabin M, Mahmood U, Chen J, Wang W, Maresca K, Waterhouse R, El Fakhri G, Richardson P, Vasdev N. Synthesis and preliminary PET imaging of 11C and 18F isotopologues of the ROS1/ALK inhibitor lorlatinib. Nature Communications 2017, 8: 15761. PMID: 28594000, PMCID: PMC5472746, DOI: 10.1038/ncomms15761.Peer-Reviewed Original ResearchMeSH KeywordsAminopyridinesAnaplastic Lymphoma KinaseAnimalsCarbon RadioisotopesChemistry Techniques, SyntheticContrast MediaFluorine RadioisotopesHumansIsotope LabelingLactamsLactams, MacrocyclicMacaca mulattaMaleMicePositron-Emission TomographyProtein-Tyrosine KinasesProto-Oncogene ProteinsPyrazolesTissue DistributionXenograft Model Antitumor AssaysConceptsAnaplastic lymphoma kinasePositron emission tomographyPositron emission tomography imagingC-ros oncogene 1Non-small cell lung cancerCell lung cancerBrain tumor lesionsOptimal therapeutic outcomesLung cancer patientsBlood-brain barrierPF-06463922Clinical trial investigatorsTumor uptakeLung cancerSmall molecule inhibitorsCancer patientsTherapeutic outcomesLorlatinibEmission tomographyDosimetry assessmentNon-human primatesTrial investigatorsBrain permeabilityEarly goalRadiolabeling strategiesPSMA-targeted contrast agents for intraoperative imaging of prostate cancer ,
Bao K, Lee J, Kang H, Park G, Fakhri G, Choi H. PSMA-targeted contrast agents for intraoperative imaging of prostate cancer ,. Chemical Communications 2017, 53: 1611-1614. PMID: 28085163, PMCID: PMC5728657, DOI: 10.1039/c6cc09781b.Peer-Reviewed Original Research
2016
Site‐Specific In Vivo Bioorthogonal Ligation via Chemical Modulation
Koo H, Lee J, Bao K, Wu Y, Fakhri G, Henary M, Yun S, Choi H. Site‐Specific In Vivo Bioorthogonal Ligation via Chemical Modulation. Advanced Healthcare Materials 2016, 5: 2510-2516. PMID: 27568818, PMCID: PMC5541365, DOI: 10.1002/adhm.201600574.Peer-Reviewed Original ResearchConceptsClick chemistryClick moietyEfficiency of click chemistryLow reaction efficiencyIn vivo click chemistryReaction efficiencyChemical structureBioorthogonal ligationMoietyChemistryBioorthogonal click chemistryNear-infrared fluorophoreChemical modulatorsSurface chargeTetrazinePharmacokinetic barriersLipophilicityControlled pharmacokineticsFluorophores
2015
Heat‐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 International Edition 2015, 54: 13002-13006. PMID: 26368132, PMCID: PMC4754124, DOI: 10.1002/anie.201505525.Peer-Reviewed Original ResearchConceptsPositron emission tomographyRadiolabelling of nanoparticlesStandardized uptake valueNP pharmacokineticsSlow uptake processUptake valueLymph nodesCirculating monocytesMonocyte traffickingIV injectionImmune responseBlood clearanceEmission tomographyHepatic uptakeMonocytesPharmacokineticsLymphUptake processCytometryImaging PEG-Like Nanoprobes in Tumor, Transient Ischemia, and Inflammatory Disease Models
Wilks M, Normandin M, Yuan H, Cho H, Guo Y, Herisson F, Ayata C, Wooten D, Fakhri G, Josephson L. Imaging PEG-Like Nanoprobes in Tumor, Transient Ischemia, and Inflammatory Disease Models. Bioconjugate Chemistry 2015, 26: 1061-1069. PMID: 25971846, PMCID: PMC5378316, DOI: 10.1021/acs.bioconjchem.5b00213.Peer-Reviewed Original Research