2024
PET imaging of M4 muscarinic acetylcholine receptors in rhesus macaques using [11C]MK-6884: Quantification with kinetic modeling and receptor occupancy by CVL-231 (emraclidine), a novel positive allosteric modulator
Belov V, Guehl N, Duvvuri S, Iredale P, Moon S, Dhaynaut M, Chakilam S, MacDonagh A, Rice P, Yokell D, Renger J, Fakhri G, Normandin M. PET imaging of M4 muscarinic acetylcholine receptors in rhesus macaques using [11C]MK-6884: Quantification with kinetic modeling and receptor occupancy by CVL-231 (emraclidine), a novel positive allosteric modulator. Cerebrovascular And Brain Metabolism Reviews 2024, 44: 1329-1342. PMID: 38477292, PMCID: PMC11342722, DOI: 10.1177/0271678x241238820.Peer-Reviewed Original ResearchConceptsPositive allosteric modulatorsReceptor occupancyNon-human primatesBinding potentialPositron emission tomographyMuscarinic acetylcholine receptorsAllosteric modulatorsNon-human primate brainM4 muscarinic acetylcholine receptorStriatal hyperdopaminergiaAcetylcholine receptorsBrain regionsCaudate nucleusTotal volume of distributionDose-dependent blockReference regionVolume of distributionPositron emission tomography imagingEmission tomographyReceptor levelsFunction of dosePET scansClinical trialsBlood-basedRhesus macaques
2023
Evaluation of trans- and cis-4‑[18F]Fluorogabapentin for Brain PET Imaging
Zhou Y, Normandin M, Belov V, Macdonald-Soccorso M, Moon S, Sun Y, Fakhri G, Guehl N, Brugarolas P. Evaluation of trans- and cis-4‑[18F]Fluorogabapentin for Brain PET Imaging. ACS Chemical Neuroscience 2023, 14: 4208-4215. PMID: 37947793, PMCID: PMC11485007, DOI: 10.1021/acschemneuro.3c00593.Peer-Reviewed Original ResearchConceptsNeuropathic painRodent models of neuropathic painSubunit of voltage-dependent calcium channelsModel of neuropathic painTreatment of neuropathic painMetabolite-corrected arterial input functionVoltage-dependent calcium channelsMultilinear analysis 1Brain uptakePET imagingDose of gabapentinOne-tissue compartment modelRegional time-activity curvesAdult rhesus macaquesPlasma protein bindingTime-activity curvesModerate brain uptakeCalcium channelsInjured nerveArterial input functionGabapentinRodent modelsAnticonvulsant medicationBrain PET imagingRhesus macaques
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
2020
Evaluation of the potassium channel tracer [18F]3F4AP in rhesus macaques
Guehl N, Ramos-Torres K, Linnman C, Moon S, Dhaynaut M, Wilks M, Han P, Ma C, Neelamegam R, Zhou Y, Popko B, Correia J, Reich D, Fakhri G, Herscovitch P, Normandin M, Brugarolas P. Evaluation of the potassium channel tracer [18F]3F4AP in rhesus macaques. Cerebrovascular And Brain Metabolism Reviews 2020, 41: 1721-1733. PMID: 33090071, PMCID: PMC8221756, DOI: 10.1177/0271678x20963404.Peer-Reviewed Original ResearchConceptsFocal brain injuryMyelin repair therapyContributions of demyelinationDrivers of disabilityImaging demyelinationBrain injuryMeasurements of molecular changesTool's sensitivity to changesLower myelin contentDemyelinating lesionsNeuronal conductionImpaired conductionDemyelinationBrain penetrationGold standardRhesus macaquesInjured areaMultiple sclerosisMolecular changesMyelin sheathNeurological diseasesHigh metabolic stabilityMRI methodsMRIInjury
2017
Synthesis 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 strategiesBrain Penetration of the ROS1/ALK Inhibitor Lorlatinib Confirmed by PET
Collier T, Maresca K, Normandin M, Richardson P, McCarthy T, Liang S, Waterhouse R, Vasdev N. Brain Penetration of the ROS1/ALK Inhibitor Lorlatinib Confirmed by PET. Molecular Imaging 2017, 16: 1536012117736669. PMID: 29067878, PMCID: PMC5661750, DOI: 10.1177/1536012117736669.Peer-Reviewed Original ResearchConceptsPositron emission tomographyLung cancerTreatment of non-small-cell lung cancerBrain metastases of patientsNon-small-cell lung cancerPositron emission tomography evaluationNonhuman primatesRodent tumor modelsGoal of clinical translationOptimal therapeutic outcomesMetastasis of patientsBlood-brain barrierBrain metastasesPF-06463922Preclinical modelsClinical trial investigatorsTumor modelMolecular alterationsLorlatinibTherapeutic outcomesCancer therapeuticsBrain penetrationClinical translationEmission tomographyTrial investigators
2014
Motion compensation for brain PET imaging using wireless MR active markers in simultaneous PET–MR: Phantom and non-human primate studies
Huang C, Ackerman J, Petibon Y, Normandin M, Brady T, Fakhri G, Ouyang J. Motion compensation for brain PET imaging using wireless MR active markers in simultaneous PET–MR: Phantom and non-human primate studies. NeuroImage 2014, 91: 129-137. PMID: 24418501, PMCID: PMC3965607, DOI: 10.1016/j.neuroimage.2013.12.061.Peer-Reviewed Original ResearchConceptsMotion correctionWireless markersList-mode reconstructionReconstructed PET imagesMotion correction techniqueObserver signal-to-noise ratioSimultaneous PET-MRMotion artifactsPET phantomPET contrastPET reconstructionBrain PET imagingPET imagingPhantomBrain PETPET-MRIndependent noise realizationsAccurate quantitative valuesHead motionNoise realizationsPET dataSignal-to-noise ratioStatic referenceBrain PET scansActivation markers
2013
Neurovascular coupling to D2/D3 dopamine receptor occupancy using simultaneous PET/functional MRI
Sander C, Hooker J, Catana C, Normandin M, Alpert N, Knudsen G, Vanduffel W, Rosen B, Mandeville J. Neurovascular coupling to D2/D3 dopamine receptor occupancy using simultaneous PET/functional MRI. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 11169-11174. PMID: 23723346, PMCID: PMC3703969, DOI: 10.1073/pnas.1220512110.Peer-Reviewed Original ResearchConceptsFunctional magnetic resonance imagingDopamine receptor occupancyReceptor occupancyPositron emission tomographyFunctional magnetic resonance imaging measuresDose of racloprideBasal dopamine levelsDopamine-rich striatumInvestigation of neurovascular couplingDomains of spaceAnesthetized nonhuman primatesSimultaneous PET/fMRIDopamine levelsBrain activitySimultaneous neuroimagingBinding potentialBasal gangliaReceptor systemNonhuman primatesPositron emission tomography tracersMagnetic resonance imagingLiterature differencesEmission tomographyMap associationsNeurovascular coupling
2012
In Vivo Imaging of Endogenous Pancreatic β-Cell Mass in Healthy and Type 1 Diabetic Subjects Using 18F-Fluoropropyl-Dihydrotetrabenazine and PET
Normandin MD, Petersen KF, Ding YS, Lin SF, Naik S, Fowles K, Skovronsky DM, Herold KC, McCarthy TJ, Calle RA, Carson RE, Treadway JL, Cline GW. In Vivo Imaging of Endogenous Pancreatic β-Cell Mass in Healthy and Type 1 Diabetic Subjects Using 18F-Fluoropropyl-Dihydrotetrabenazine and PET. Journal Of Nuclear Medicine 2012, 53: 908-916. PMID: 22573821, PMCID: PMC3737743, DOI: 10.2967/jnumed.111.100545.Peer-Reviewed Original ResearchConceptsType 1 diabetes mellitusVesicular monoamine transporter type 2Pancreatic β-cell massStandardized uptake valueΒ-cell massDiabetes mellitusUptake valueType 1 diabetic subjectsΒ-cell densityHealthy control subjectsInsulin secretion capacityΒ-cell functionPathophysiology of diabetesTransporter type 2Nondisplaceable uptakeDiabetic subjectsControl subjectsDisease progressionClinical assessmentVMAT2 bindingRenal cortexTotal pancreasDTBZ PETEarly diagnosisInjected dose