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
2022
PET 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 ligandsSynthesis 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
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