2024
PET mapping of receptor occupancy using joint direct parametric reconstruction
Marin T, Belov V, Chemli Y, Ouyang J, Najmaoui Y, Fakhri G, Duvvuri S, Iredale P, Guehl N, Normandin M, Petibon Y. PET mapping of receptor occupancy using joint direct parametric reconstruction. IEEE Transactions On Biomedical Engineering 2024, PP: 1-15. PMID: 39446540, DOI: 10.1109/tbme.2024.3486191.Peer-Reviewed Original ResearchCentral nervous systemReceptor occupancyLow-binding regionsPET scansSimulation resultsPreclinical in vivo experimentsDynamic PET scansPairs of baselineEstimation of receptor occupancyEstimation frameworkPET neuroimagingReconstruction frameworkModulating drugsTime activity curvesParametric reconstructionDevelopment of drugsPET 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
2022
Human biodistribution and radiation dosimetry of the demyelination tracer [18F]3F4AP
Brugarolas P, Wilks M, Noel J, Kaiser J, Vesper D, Ramos-Torres K, Guehl N, Macdonald-Soccorso M, Sun Y, Rice P, Yokell D, Lim R, Normandin M, El Fakhri G. Human biodistribution and radiation dosimetry of the demyelination tracer [18F]3F4AP. European Journal Of Nuclear Medicine And Molecular Imaging 2022, 50: 344-351. PMID: 36197499, PMCID: PMC9816249, DOI: 10.1007/s00259-022-05980-w.Peer-Reviewed Original ResearchConceptsRadiation dosimetryTime-activity curvesAdverse eventsEffective doseMultiple bed positionsComprehensive metabolic panelNonhuman primatesHealthy human volunteersNo adverse eventsDynamic PET scansVoltage-gated potassiumAnimal models of neurological diseasesNonhuman primate studiesModels of neurological diseasesHuman biodistributionAverage effective doseMetabolic panelDosimetryOLINDA softwareHealthy volunteersUrinary bladderPET scansDemyelinating lesionsBed positionAnimal models
2019
Evaluation of pharmacokinetic modeling strategies for in-vivo quantification of tau with the radiotracer [18F]MK6240 in human subjects
Guehl N, Wooten D, Yokell D, Moon S, Dhaynaut M, Katz S, Moody K, Gharagouzloo C, Kas A, Johnson K, El Fakhri G, Normandin M. Evaluation of pharmacokinetic modeling strategies for in-vivo quantification of tau with the radiotracer [18F]MK6240 in human subjects. European Journal Of Nuclear Medicine And Molecular Imaging 2019, 46: 2099-2111. PMID: 31332496, PMCID: PMC6709592, DOI: 10.1007/s00259-019-04419-z.Peer-Reviewed Original ResearchConceptsReference tissue methodDistribution volume ratioTissue methodIn vivo quantificationPharmacokinetic modeling strategiesArterial plasma input functionMultilinear reference tissue methodsTwo-tissue compartment modelBlood:plasma ratioTissue-to-plasmaPlasma input functionPlasma concentration time courseBlood-based methodMethodsThirty-five subjectsSUV ratioBlood-based analysesData setsArterial input functionPET scansControl subjectsMild cognitive impairmentPlasma ratioRadiometabolite analysisHealthy controlsConcentration time course
2017
Pseudoreference Regions for Glial Imaging with 11C-PBR28: Investigation in 2 Clinical Cohorts
Albrecht D, Normandin M, Shcherbinin S, Wooten D, Schwarz A, Zürcher N, Barth V, Guehl N, Akeju O, Atassi N, Veronese M, Turkheimer F, Hooker J, Loggia M. Pseudoreference Regions for Glial Imaging with 11C-PBR28: Investigation in 2 Clinical Cohorts. Journal Of Nuclear Medicine 2017, 59: 107-114. PMID: 28818984, PMCID: PMC5750517, DOI: 10.2967/jnumed.116.178335.Peer-Reviewed Original ResearchConceptsChronic low back painPseudoreference regionGroup differencesDistribution volume ratioOccipital cortexArterial input functionChronic low back pain patientsAbsence of group differencesNo significant group differencesTranslocator protein imagingLow back painRegional group differencesSignificant group differencesAmyotrophic lateral sclerosisTranslocator proteinMatched healthy controlsDetect group differencesWithin-group variabilityBack painNeuroimmune activationVoxelwise analysisPET scansHealthy controlsClinical cohortDistribution volume