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