2022
Design, Synthesis, and Characterization of [18F]mG2P026 as a High-Contrast PET Imaging Ligand for Metabotropic Glutamate Receptor 2
Yuan G, Dhaynaut M, Guehl N, Afshar S, Huynh D, Moon S, Iyengar S, Jain M, Pickett J, Kang H, Ondrechen M, Fakhri G, Normandin M, Brownell A. Design, Synthesis, and Characterization of [18F]mG2P026 as a High-Contrast PET Imaging Ligand for Metabotropic Glutamate Receptor 2. Journal Of Medicinal Chemistry 2022, 65: 9939-9954. PMID: 35802702, PMCID: PMC9434700, DOI: 10.1021/acs.jmedchem.2c00593.Peer-Reviewed Original ResearchConceptsPositive allosteric modulatorsMetabotropic glutamate receptor 2Glutamate receptor 2Cu-mediated radiofluorinationPET imaging ligandsReceptor 2High molar activityExcellent radiochemical purityGloSensor assayPositron emission tomography radiotracersClasses of positive allosteric modulatorsNon-human primatesJNJ-46356479Radiochemical yieldBrain heterogeneityAllosteric modulatorsBrain uptakeMGluR2Molar activityLigandBrainBrain permeabilityImaging ligandsBinding kineticsMetabotropic
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 subtypesCompoundsBindingSynthesis and Characterization of Fluorine-18-Labeled N‑(4-Chloro-3-((fluoromethyl‑d 2)thio)phenyl)picolinamide for Imaging of mGluR4 in Brain
Wang J, Qu X, Shoup T, Yuan G, Afshar S, Pan C, Zhu A, Choi J, Kang H, Poutiainen P, Fakhri G, Zhang Z, Brownell A. Synthesis and Characterization of Fluorine-18-Labeled N‑(4-Chloro-3-((fluoromethyl‑d 2)thio)phenyl)picolinamide for Imaging of mGluR4 in Brain. Journal Of Medicinal Chemistry 2020, 63: 3381-3389. PMID: 32081008, PMCID: PMC7261135, DOI: 10.1021/acs.jmedchem.0c00201.Peer-Reviewed Original ResearchConceptsDrug-like propertiesMethylthio analoguePotential ligandsMetabolic stabilityPositron emission tomographyRadiochemical yieldMolar activityDose-dependent blocking effectPositron emission tomography imaging studiesMethylthioPAM activityBrain regionsMale Sprague Dawley ratsLigandEx vivo biodistribution studiesRadiosynthesisSprague Dawley ratsBrainMGluR4SynthesisAnaloguesEmission tomographyImaging studiesA 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
2017
A report of the automated radiosynthesis of the tau positron emission tomography radiopharmaceutical, [18F]‐THK‐5351
Neelamegam R, Yokell D, Rice P, Furumoto S, Kudo Y, Okamura N, Fakhri G. A report of the automated radiosynthesis of the tau positron emission tomography radiopharmaceutical, [18F]‐THK‐5351. Journal Of Labelled Compounds And Radiopharmaceuticals 2017, 60: 140-146. PMID: 27859483, DOI: 10.1002/jlcr.3482.Peer-Reviewed Original ResearchConceptsO-THPNucleophilic fluorination reactionsHydrochloric acidFluorination reactionDilute hydrochloric acidSemi-preparative high-performance liquid chromatographyTosylate precursorHigh-performance liquid chromatographyUncorrected radiochemical yieldDimethyl sulfoxideRadiochemical yieldRadiosynthesis moduleMulti-center trialLiquid chromatographyAutomated radiosynthesisRadiosynthesisPositron emission tomography radiopharmaceuticalsPET imaging agentUnited States Pharmacopeia
2014
First Human Use of a Radiopharmaceutical Prepared by Continuous-Flow Microfluidic Radiofluorination: Proof of Concept with the Tau Imaging Agent [18F]T807
Liang S, Yokell D, Normandin M, Rice P, Jackson R, Shoup T, Brady T, Fakhri G, Collier T, Vasdev N. First Human Use of a Radiopharmaceutical Prepared by Continuous-Flow Microfluidic Radiofluorination: Proof of Concept with the Tau Imaging Agent [18F]T807. Molecular Imaging 2014, 13: 7290.2014.00025. PMID: 25248283, DOI: 10.2310/7290.2014.00025.Peer-Reviewed Original Research