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 strategies
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
Dual-Tracer PET Using Generalized Factor Analysis of Dynamic Sequences
El Fakhri G, Trott C, Sitek A, Bonab A, Alpert N. Dual-Tracer PET Using Generalized Factor Analysis of Dynamic Sequences. Molecular Imaging And Biology 2013, 15: 666-674. PMID: 23636489, PMCID: PMC3812387, DOI: 10.1007/s11307-013-0631-1.Peer-Reviewed Original ResearchConceptsEmit gamma raysPositron emission tomographyNear-simultaneous imagingSingle-photon emissionBrain PET studiesGamma raysSingle-photon emission computed tomographyActivity distributionRaclopride studiesEmission computed tomographyPositron emission tomography radiopharmaceuticalsSimultaneous imagingD2 bindingFactor analysis of dynamic sequencesActivity estimationTime activity curvesRacloprideFDGRhesus monkeysEmission tomographyPET studiesActivation curveBrain metabolismEmissionSimulate human data
2012
MRI-Based Nonrigid Motion Correction in Simultaneous PET/MRI
Chun Y, Reese T, Ouyang J, Guerin B, Catana C, Zhu X, Alpert N, Fakhri G. MRI-Based Nonrigid Motion Correction in Simultaneous PET/MRI. Journal Of Nuclear Medicine 2012, 53: 1284-1291. PMID: 22743250, PMCID: PMC4077320, DOI: 10.2967/jnumed.111.092353.Peer-Reviewed Original ResearchConceptsChannelized Hotelling observerMotion correctionDetection signal-to-noise ratioSignal-to-noise ratioMRI-based motion correctionRespiratory motion correctionMotion-corrected reconstructionOrdered-subsets expectation maximization algorithmNonrigid motion correctionChannelized Hotelling observer studyPET image qualityNonrigid image registration methodCoincidence dataDeformable phantomRespiratory gatingReduce radiation doseDynamic phantomImage registration methodReduced signal-to-noise ratioSimultaneous PET/MRICost of increased noiseHotelling observerPhantomAttenuation measurementsRabbit studies