2024
Radiosynthesis 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
Measurement of Cerebral Perfusion Indices from the Early Phase of [18F]MK6240 Dynamic Tau PET Imaging
Guehl N, Dhaynaut M, Hanseeuw B, Moon S, Lois C, Thibault E, Fu J, Price J, Johnson K, El Fakhri G, Normandin M. Measurement of Cerebral Perfusion Indices from the Early Phase of [18F]MK6240 Dynamic Tau PET Imaging. Journal Of Nuclear Medicine 2023, 64: 968-975. PMID: 36997330, PMCID: PMC10241011, DOI: 10.2967/jnumed.122.265072.Peer-Reviewed Original ResearchConceptsTime-activity curvesCerebral perfusionMetabolite-corrected arterial input functionBrain time-activity curvesEarly phaseRegional time-activity curvesIndices of cerebral perfusionDynamic [<sup>18</sup>FBlood-brain barrierPlasma to brain tissueStatistically significant differenceArterial blood samplesForty-nine subjectsCNArterial input functionPathophysiological mechanismsPerfusion indicatorsPET imagingBlood samplesSignificant differenceSurrogate indexNoninvasive estimationAnatomical informationCompound BForty-nine
2022
PET imaging of mitochondrial function in acute doxorubicin-induced cardiotoxicity: a proof-of-principle study
Detmer F, Alpert N, Moon S, Dhaynaut M, Guerrero J, Guehl N, Xing F, Brugarolas P, Shoup T, Normandin M, Pelletier-Galarneau M, El Fakhri G, Petibon Y. PET imaging of mitochondrial function in acute doxorubicin-induced cardiotoxicity: a proof-of-principle study. Scientific Reports 2022, 12: 6122. PMID: 35414642, PMCID: PMC9005533, DOI: 10.1038/s41598-022-10004-6.Peer-Reviewed Original ResearchConceptsLeft anterior descending coronary arteryDoxorubicin-induced cardiotoxicityCardiac membrane potentialDoxorubicin infusionMembrane potentialAnimal modelsAcute doxorubicin-induced cardiotoxicityLeft anterior descending coronary artery territoryAcute cardiotoxic effectsAnterior descending coronary arteryControl saline infusionDescending coronary arteryDoxorubicin doseSaline infusionTest infusionCardiotoxic effectsMitochondrial membrane potentialInfusion catheterCoronary arteryInfusionMitochondrial functionDoxorubicinMyocardial areaPET imagingIntracoronary catheterImpact 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 clearanceSynthesis and Characterization of 5‑(2-Fluoro-4‑[11C]methoxyphenyl)-2,2-dimethyl-3,4-dihydro‑2H‑pyrano[2,3‑b]pyridine-7-carboxamide as a PET Imaging Ligand for Metabotropic Glutamate Receptor 2
Yuan G, Dhaynaut M, Lan Y, Guehl N, Huynh D, Iyengar S, Afshar S, Jain M, Pickett J, Kang H, Wang H, Moon S, Ondrechen M, Wang C, Shoup T, Fakhri G, Normandin M, Brownell A. Synthesis and Characterization of 5‑(2-Fluoro-4‑[11C]methoxyphenyl)-2,2-dimethyl-3,4-dihydro‑2H‑pyrano[2,3‑b]pyridine-7-carboxamide as a PET Imaging Ligand for Metabotropic Glutamate Receptor 2. Journal Of Medicinal Chemistry 2022, 65: 2593-2609. PMID: 35089713, PMCID: PMC9434702, DOI: 10.1021/acs.jmedchem.1c02004.Peer-Reviewed Original ResearchConceptsNegative allosteric modulatorsMetabotropic glutamate receptor 2Positron emission tomographyGlutamate receptor 2MGluR2 functionNeuropsychiatric disordersDrug effectsBrain heterogeneityReceptor 2Allosteric modulatorsMGluR2Nonhuman primatesBrain imagingPositron emission tomography imagingPositron emission tomography imaging ligandsHigh molar activityEmission tomographyExcellent radiochemical purityImaging ligandsBlocking agentsPET imagingMolar activityTherapeutic targetMetabotropicDisorders
2021
Evaluation 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 assayClearance