2024
Advances and Insights in Positron Emission Tomography Tracers for Metabotropic Glutamate Receptor 4 Imaging
Wang J, Li Y, Fakhri G. Advances and Insights in Positron Emission Tomography Tracers for Metabotropic Glutamate Receptor 4 Imaging. Journal Of Medicinal Chemistry 2024, 67: 10517-10529. PMID: 38924702, PMCID: PMC11290609, DOI: 10.1021/acs.jmedchem.3c02431.Peer-Reviewed Original ResearchConceptsPositive allosteric modulatorsPositron emission tomographyPositron emission tomography radioligandsAllosteric modulatorsMGluR4 positive allosteric modulatorsMetabotropic glutamate receptor subtype 4PET ligandNeurological disordersPositron emission tomography tracersEmission tomographySubtype 4Molecular imaging modalitiesEffective treatmentMetabotropicDisordersParent drugImaging modalitiesPET tracersMGluR4Therapeutic targetPositron emitting radioisotopesSelection of lead compoundsLiving subjectsPositronQuantitative accuracy
2022
A multi-pronged investigation of option generation using depression, PET and modafinil
Ang Y, Cusin C, Petibon Y, Dillon D, Breiger M, Belleau E, Normandin M, Schroder H, Boyden S, Hayden E, Levine M, Jahan A, Meyer A, Kang M, Brunner D, Gelda S, Hooker J, Fakhri G, Fava M, Pizzagalli D. A multi-pronged investigation of option generation using depression, PET and modafinil. Brain 2022, 145: 1854-1865. PMID: 35150243, PMCID: PMC9166534, DOI: 10.1093/brain/awab429.Peer-Reviewed Original ResearchConceptsD2/D3 receptor availabilitySelf-generated optionsDepressive disorderDepressed individualsReceptor availabilityDopamine D2/D3 receptor availabilityNon-depressed adultsEffects of modafinilPutamen of patientsAssociated with uniquenessOption generationD2/D3 receptorsDopaminergic activityClinical depressionBinding potentialModafinilHealthy participantsPutamenPlacebo-controlledSamples of healthy peopleDouble-blindDisordersSelf-generationHealthy controlsDopamineSynthesis 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
In vivo imaging of mGlu5 receptor expression in humans with Fragile X Syndrome towards development of a potential biomarker
Mody M, Petibon Y, Han P, Kuruppu D, Ma C, Yokell D, Neelamegam R, Normandin M, Fakhri G, Brownell A. In vivo imaging of mGlu5 receptor expression in humans with Fragile X Syndrome towards development of a potential biomarker. Scientific Reports 2021, 11: 15897. PMID: 34354107, PMCID: PMC8342610, DOI: 10.1038/s41598-021-94967-y.Peer-Reviewed Original ResearchConceptsFragile X syndromeFragile X mental retardation proteinX syndromeLoss of fragile X mental retardation proteinMGlu5 receptor expressionMetabotropic glutamate subtype 5 receptorsDrug occupancy studiesSignificant group differencesFragile X mental retardationHealthy controlsAnterior cingulateMGluR5 availabilityVisuospatial processingMGlu5 receptorsOlfactory cortexBrain areasGroup differencesRetardation proteinGlutamate signalingImages of maleNeurodevelopmental disordersExcessive glutamate signalingGender-matched controlsDisordersMGluR5Exploring Gender Differences in the Placebo Response to Major Depressive Disorder (MDD) Using Neuroimaging Techniques
Jahan A, Dillon D, Petibon Y, Meyer A, Normandin M, Belleau E, Alpert N, Fakhri G, Hooker J, Crowley D, Cusin C, Pizzagalli D, Fava M. Exploring Gender Differences in the Placebo Response to Major Depressive Disorder (MDD) Using Neuroimaging Techniques. Biological Psychiatry 2021, 89: s171-s172. DOI: 10.1016/j.biopsych.2021.02.438.Peer-Reviewed Original ResearchSynthesis 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