2022
Radiochemical Synthesis and Evaluation of 3‑[11C]Methyl-4-aminopyridine in Rodents and Nonhuman Primates for Imaging Potassium Channels in the CNS
Sun Y, Guehl N, Zhou Y, Takahashi K, Belov V, Dhaynaut M, Moon S, Fakhri G, Normandin M, Brugarolas P. Radiochemical Synthesis and Evaluation of 3‑[11C]Methyl-4-aminopyridine in Rodents and Nonhuman Primates for Imaging Potassium Channels in the CNS. ACS Chemical Neuroscience 2022, 13: 3342-3351. PMID: 36417797, PMCID: PMC9732819, DOI: 10.1021/acschemneuro.2c00364.Peer-Reviewed Original ResearchConceptsRegional brain time-activity curvesBrain time-activity curvesOne-tissue compartment modelBlood-brain barrierConsistent with <i>inNonhuman primatesTime-activity curvesPositron emission tomographySpinal cord injuryDemyelinated neuronsNeurological symptomsPotassium channelsNeuronal conductionBrain uptakeEmission tomographyStille cross-couplingMultiple sclerosisCord injurySlow kineticsBrain permeabilityTraumatic brainMyelin sheathStronger binding affinityNeuronsBrainPET imaging studies to investigate functional expression of mGluR2 using [11C]mG2P001
Yuan G, Dhaynaut M, Guehl N, Neelamegam R, Moon S, Qu X, Poutiainen P, Afshar S, Fakhri G, Normandin M, Brownell A. PET imaging studies to investigate functional expression of mGluR2 using [11C]mG2P001. Cerebrovascular And Brain Metabolism Reviews 2022, 43: 296-308. PMID: 36172629, PMCID: PMC9903221, DOI: 10.1177/0271678x221130387.Peer-Reviewed Original ResearchConceptsPositive allosteric modulatorsPositron emission tomographyNon-human primatesMGluR2 positive allosteric modulatorPositron emission tomography imagingPositive allosteric modulator of mGluR2Metabotropic glutamate receptor 2Positron emission tomography imaging studiesExpression of mGluR2Glutamate receptor 2MGluR2 functionPsychiatric disordersMGluR2 expressionTissue glutamate concentrationMGluR2Expressing mGluR2Allosteric modulatorsRat brainTransfected CHO cellsReceptor 2Glutamate concentrationEmission tomographyImaging studiesPharmacological effectsImaging ligandsDesign, 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 kineticsMetabotropicSynthesis 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
Neurovascular imaging with QUTE-CE MRI in APOE4 rats reveals early vascular abnormalities
Leaston J, Ferris C, Kulkarni P, Chandramohan D, van de Ven A, Qiao J, Timms L, Sepulcre J, Fakhri G, Ma C, Normandin M, Gharagouzloo C. Neurovascular imaging with QUTE-CE MRI in APOE4 rats reveals early vascular abnormalities. PLOS ONE 2021, 16: e0256749. PMID: 34449808, PMCID: PMC8396782, DOI: 10.1371/journal.pone.0256749.Peer-Reviewed Original ResearchConceptsVascular abnormalitiesAPOE-e4Contrast-enhanced magnetic resonance imagingBlood-brain-barrier leakageNeurovascular dysfunctionSmall vessel abnormalitiesMagnetic resonance imagingTri-synaptic circuitBlood-brain-barrierCross-sectional studyFemale ratsSignificant signal increaseHyper-vascularizationCerebrovascular abnormalitiesVessel abnormalitiesNeurovascular imagingQUTE-CEBrain volumeAnimal modelsPathological causesAbnormalitiesHistological validationImaging modalitiesResonance imagingSynthesis 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
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
2015
Imaging 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
2011
Synthesis and evaluation of [18F]exendin (9–39) as a potential biomarker to measure pancreatic β-cell mass
Wang Y, Lim K, Normandin M, Zhao X, Cline GW, Ding YS. Synthesis and evaluation of [18F]exendin (9–39) as a potential biomarker to measure pancreatic β-cell mass. Nuclear Medicine And Biology 2011, 39: 167-176. PMID: 22033026, PMCID: PMC4484741, DOI: 10.1016/j.nucmedbio.2011.07.011.Peer-Reviewed Original ResearchConceptsStandardized uptake valuePositron emission tomography (PET) imagingEmission Tomography ImagingPancreatic β-cell massΒ-cell massTomography imagingInsulin contentGlucagon-like peptide-1 (GLP-1) receptor antagonistGlucagon-like peptide-1Biobreeding diabetes-prone (BB-DP) ratDiabetes-prone ratsVivo positron emission tomography (PET) imagingSprague-Dawley ratsBlood glucose homeostasisReceptor antagonistGlucose homeostasisPeptide-1Time-activity curvesUptake valuePotential biomarkersHigh-resolution research tomographExendin analogsIn-111RatsPostmortem measuresA linear model for estimation of neurotransmitter response profiles from dynamic PET data
Normandin MD, Schiffer WK, Morris ED. A linear model for estimation of neurotransmitter response profiles from dynamic PET data. NeuroImage 2011, 59: 2689-2699. PMID: 21767654, PMCID: PMC3702051, DOI: 10.1016/j.neuroimage.2011.07.002.Peer-Reviewed Original ResearchImaging of alcohol‐induced dopamine release in rats:Preliminary findings with [11C]raclopride PET
Sullivan JM, Risacher SL, Normandin MD, Yoder KK, Froehlich JC, Morris ED. Imaging of alcohol‐induced dopamine release in rats:Preliminary findings with [11C]raclopride PET. Synapse 2011, 65: 929-937. PMID: 21308803, PMCID: PMC3130821, DOI: 10.1002/syn.20921.Peer-Reviewed Original ResearchConceptsPositron emission tomographyBlood alcohol concentrationSmall animal positron emission tomographyRat striatumAnimal positron emission tomographyP ratsAlcohol-induced dopamine releaseSignificant alcohol-induced decreaseAlcohol-induced decreaseBlood alcohol levelsLateral saphenous veinAlcohol-preferring ratsAnimals 10 minSystemic alcoholDA releaseMicrodialysis studyStriatal dopamineAlcohol administrationSaphenous veinMale WistarDopamine releaseLarge cohortExtracellular dopamineBlood samplesReceptor availability
2010
Pancreatic Beta Cell Mass PET Imaging and Quantification with [11C]DTBZ and [18F]FP-(+)-DTBZ in Rodent Models of Diabetes
Singhal T, Ding YS, Weinzimmer D, Normandin MD, Labaree D, Ropchan J, Nabulsi N, Lin SF, Skaddan MB, Soeller WC, Huang Y, Carson RE, Treadway JL, Cline GW. Pancreatic Beta Cell Mass PET Imaging and Quantification with [11C]DTBZ and [18F]FP-(+)-DTBZ in Rodent Models of Diabetes. Molecular Imaging And Biology 2010, 13: 973-984. PMID: 20824509, PMCID: PMC3711476, DOI: 10.1007/s11307-010-0406-x.Peer-Reviewed Original Research
2008
A rat head holder for simultaneous scanning of two rats in small animal PET scanners: Design, construction, feasibility testing and kinetic validation
Cheng TE, Yoder KK, Normandin MD, Risacher SL, Converse AK, Hampel JA, Miller MA, Morris ED. A rat head holder for simultaneous scanning of two rats in small animal PET scanners: Design, construction, feasibility testing and kinetic validation. Journal Of Neuroscience Methods 2008, 176: 24-33. PMID: 18824025, PMCID: PMC3725621, DOI: 10.1016/j.jneumeth.2008.08.031.Peer-Reviewed Original ResearchInitial Comparison of ntPET with Microdialysis Measurements of Methamphetamine-Induced Dopamine Release in Rats: Support for Estimation of Dopamine Curves from PET Data
Morris ED, Normandin MD, Schiffer WK. Initial Comparison of ntPET with Microdialysis Measurements of Methamphetamine-Induced Dopamine Release in Rats: Support for Estimation of Dopamine Curves from PET Data. Molecular Imaging And Biology 2008, 10: 67-73. PMID: 18176804, DOI: 10.1007/s11307-007-0124-1.Peer-Reviewed Original Research
2005
ntPET: A New Application of PET Imaging for Characterizing the Kinetics of Endogenous Neurotransmitter Release
Morris ED, Yoder KK, Wang C, Normandin MD, Zheng QH, Mock B, Raymond F, Froehlich JC. ntPET: A New Application of PET Imaging for Characterizing the Kinetics of Endogenous Neurotransmitter Release. Molecular Imaging 2005, 4: 7290.2005.05130. PMID: 16285909, DOI: 10.2310/7290.2005.05130.Peer-Reviewed Original ResearchConceptsNeurotransmitter releaseArterial blood samplingEndogenous neurotransmitter releasePositron emission tomographyEndogenous dopamineDrug treatmentRat striatumBlood samplingBlood flowEmission tomographyFalse-positive responsesD3 receptor ligandsDopamine concentrationsPET imagingReceptor ligandsNoninvasive assayTracer kinetic modelReference regionStimulus conditionsDopamine