2025
Simplified methods for SERT occupancy estimation measured with [11C]DASB PET bolus plus infusion
Ponce de León M, Murgaš M, Silberbauer L, Hacker M, Gryglewski G, Hahn A, Lanzenberger R. Simplified methods for SERT occupancy estimation measured with [11C]DASB PET bolus plus infusion. NeuroImage 2025, 311: 121208. PMID: 40221064, DOI: 10.1016/j.neuroimage.2025.121208.Peer-Reviewed Original ResearchSerotonin transporterBolus plus constant infusionSerotonin transporter occupancyDepressive disorderBinding potentialBolus plus infusionReference regionCitalopramHealthy controlsArterial blood samplesPET/MRI scansPET scansOccupational valuesIntravenous applicationConstant infusionBlood samplesIn vivoAntidepressantsInfusionSaline solutionSerotoninHighest agreementDisordersRadioligandPlaceboEffects of Long-Term Cocaine Self-Administration on Kappa Opioid Receptors in Socially Housed Cynomolgus Monkeys as Assessed with PET Imaging and Neuronally Derived Exosomes
Johnson B, Allen M, Nader S, Sai K, Kumar A, Su Y, Singh S, Li S, Huang Y, Deep G, Nader M. Effects of Long-Term Cocaine Self-Administration on Kappa Opioid Receptors in Socially Housed Cynomolgus Monkeys as Assessed with PET Imaging and Neuronally Derived Exosomes. Biological Psychiatry 2025 PMID: 40054763, DOI: 10.1016/j.biopsych.2025.02.900.Peer-Reviewed Original ResearchLong-term cocaine self-administrationKappa-opioid receptorsCocaine self-administrationSelf-administrationKappa opioid receptor availabilityPeripheral measuresSocially housed monkeysOpioid receptorsCocaine intakeCocaine SAIntravenous cocaineCocaine misuseBrain regionsCocainePET imagingCynomolgus monkeysSocial rankPET studiesPharmacological interventionsMonkeysPET scansBrainBlood samplesDominant femalesSocialPET 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 2025, 72: 1057-1066. PMID: 39446540, PMCID: PMC11875991, 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 drugsSelective Mu-Opioid Receptor Imaging Using 18F‑Labeled Carfentanils
Lee S, Pearson T, Dhaynaut M, MacDonagh A, Wey H, Wilks M, Roth B, Hooker J, Normandin M. Selective Mu-Opioid Receptor Imaging Using 18F‑Labeled Carfentanils. Journal Of Medicinal Chemistry 2025, 68: 1632-1644. PMID: 39772615, DOI: 10.1021/acs.jmedchem.4c02287.Peer-Reviewed Original ResearchConceptsMu-opioid receptorsPositron emission tomographyIn vivo PET scansCarbon-11Neurobiological studiesCopper-mediated radiofluorinationMu-opioidReceptor imagingPET scansBrain uptakeFavorable pharmacokineticsImaging evaluationHigh molar activityMass doseEmission tomographyHalf-life of fluorine-18Synthetic opioidsFluorine-18Half-lifeIn vitro binding assaysBinding assaysClinical research useMolar activityCarfentanilResearch use
2024
Exploration of (R)-[11C]YH168 as a PET tracer for imaging monoacylglycerol lipase in the brain: from mice to non-human primates
He Y, Zheng M, Gu J, Reichert L, Trimborn J, Zhang H, Keller C, Crosby M, Collin L, Heer D, Pavlovic A, Topp A, Wittwer M, Grether U, Gobbi L, Schibli R, Huang Y, Mu L. Exploration of (R)-[11C]YH168 as a PET tracer for imaging monoacylglycerol lipase in the brain: from mice to non-human primates. European Journal Of Nuclear Medicine And Molecular Imaging 2024, 52: 1556-1565. PMID: 39673602, PMCID: PMC11839854, DOI: 10.1007/s00259-024-07013-0.Peer-Reviewed Original ResearchMonoacylglycerol lipaseNon-human primatesIn vitro autoradiographyBrain regionsMice to non-human primatesMAGL knockoutNon-displaceable binding potentialRhesus monkeysNon-human primate brainRegional non-displaceable binding potentialsRegional time-activity curvesMouse brainCingulate cortexFrontal cortexEndocannabinoid systemLevels of radioactive uptakeMouse brain slicesOccipital cortexBrains of miceOne-tissue compartment modelBinding potentialMAGL expressionPET scansKnockout micePrimate brainNon-dominant, Non-lesional Mesial Temporal Lobe Epilepsy
Herlopian A, Mattson R. Non-dominant, Non-lesional Mesial Temporal Lobe Epilepsy. 2024, 63-86. DOI: 10.1007/978-3-031-23828-4_4.Peer-Reviewed Original ResearchTemporal lobe epilepsyLobe epilepsySurgical outcomesMRI-negative temporal lobe epilepsyInterictal PET scanPharmacoresistant temporal lobe epilepsyPost-operative resultsFavorable post-operative resultsTemporal lobe seizuresSlow wave activityMRI-negativePET scansHypermotor symptomsPharmacoresistant epilepsyRespiratory manifestationsNon-lesionalFronto-parietal cortexPatientsEpilepsyImpaired awarenessNon-dominant, Non-lesional Orbitofrontal-Plus Epilepsy
Herlopian A. Non-dominant, Non-lesional Orbitofrontal-Plus Epilepsy. 2024, 563-598. DOI: 10.1007/978-3-031-23828-4_23.Peer-Reviewed Original ResearchResection surgeryIntracranial monitoringInterictal PET scanIctal onset patternsPost-operative outcomesNon-lesional epilepsySurgical work-upInterictal epileptiform dischargesNon-invasive modalityDelta slowingEEG findingsInvestigative armamentariumTonic seizuresEpileptiform dischargesPET scansIctal propagationWidespread hypometabolismWork-upInsular epilepsyPsychiatric manifestationsOnset patternsSpike rateEpilepsySurgeryPatientsPET 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
Tau epicenter identification and connectivity in clinically heterogeneous Alzheimer’s disease variants
Trainer A, Xu W, Chase A, O'Dell R, Tun S, Li J, Ju S, van Dyck C, Mecca A, Fredricks C. Tau epicenter identification and connectivity in clinically heterogeneous Alzheimer’s disease variants. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.079435.Peer-Reviewed Original ResearchAmnestic Alzheimer's diseaseLogopenic variant primary progressive aphasiaPosterior cortical atrophyFunctional connectivity mapsHigher tau burdenFunctional connectivityTau burdenAlzheimer's diseaseConnectivity mapsLongitudinal tau-PETSpread of tauVariant primary progressive aphasiaFusiform gyrusFrontal eye fieldPrimary progressive aphasiaBrains of participantsTau PET scansSuperior parietal lobulePatient-specific biomarkersCortical atrophyCommon subtypeTau-PETHealthy controlsParietooccipital cortexPET scansGastroesophageal junction adenocarcinoma 1-year after sleeve gastrectomy
Brown K, Esnaola G, Boffa D, Morton J. Gastroesophageal junction adenocarcinoma 1-year after sleeve gastrectomy. Journal Of Surgical Case Reports 2023, 2023: rjad518. PMID: 37771883, PMCID: PMC10532088, DOI: 10.1093/jscr/rjad518.Peer-Reviewed Original ResearchSleeve gastrectomyUnderwent laparoscopic sleeve gastrectomyLaparoscopic sleeve gastrectomyGastroesophageal junction adenocarcinomaEsophageal stent placementMonths postopTotal gastrectomyY esophagojejunostomyDistal esophagectomyDistal esophagusEsophageal massJunction adenocarcinomaNormal endoscopyGastroesophageal junctionGastroesophageal malignanciesNegative marginsSevere stenosisStent placementInvasive adenocarcinomaCircumferential massGastrectomyRadiation therapyPET scansAdenocarcinomaLocalized perforationA Multivariate Method for Estimating and comparing whole brain functional connectomes from fMRI and PET data
Saha D, Bohsali A, Saha R, Hajjar I, Calhoun V. A Multivariate Method for Estimating and comparing whole brain functional connectomes from fMRI and PET data. Annual International Conference Of The IEEE Engineering In Medicine And Biology Society (EMBC) 2023, 00: 1-4. PMID: 38083351, DOI: 10.1109/embc40787.2023.10340631.Peer-Reviewed Original ResearchConceptsWhole-brain functional connectomePositron emission tomographyResting fMRIResting fMRI dataBrain positron emission tomographyBrain functional connectomePositron emission tomography dataResting networksMagnetic resonance imagingConnectomeFunctional connectomeBrain networksConnectome patternsFMRIFMRI dataBrain functionSubject expressionPiB-PET scansBrainEmission tomographySpatial mappingSpatial networksClinical Relevance-This studyPET scansResonance imagingLongitudinal head-to-head comparison of 11C-PiB and 18F-florbetapir PET in a Phase 2/3 clinical trial of anti-amyloid-β monoclonal antibodies in dominantly inherited Alzheimer’s disease
Chen C, McCullough A, Gordon B, Joseph-Mathurin N, Flores S, McKay N, Hobbs D, Hornbeck R, Fagan A, Cruchaga C, Goate A, Perrin R, Wang G, Li Y, Shi X, Xiong C, Pontecorvo M, Klein G, Su Y, Klunk W, Jack C, Koeppe R, Snider B, Berman S, Roberson E, Brosch J, Surti G, Jiménez-Velázquez I, Galasko D, Honig L, Brooks W, Clarnette R, Wallon D, Dubois B, Pariente J, Pasquier F, Sanchez-Valle R, Shcherbinin S, Higgins I, Tunali I, Masters C, van Dyck C, Masellis M, Hsiung R, Gauthier S, Salloway S, Clifford D, Mills S, Supnet-Bell C, McDade E, Bateman R, Benzinger T. Longitudinal head-to-head comparison of 11C-PiB and 18F-florbetapir PET in a Phase 2/3 clinical trial of anti-amyloid-β monoclonal antibodies in dominantly inherited Alzheimer’s disease. European Journal Of Nuclear Medicine And Molecular Imaging 2023, 50: 2669-2682. PMID: 37017737, PMCID: PMC10330155, DOI: 10.1007/s00259-023-06209-0.Peer-Reviewed Original ResearchConceptsStandardized uptake value ratioPhase 2/3 clinical trialsPositron emission tomographyAnti-Aβ monoclonal antibodyClinical trialsPlacebo armDrug effectsLongitudinal changesMonoclonal antibodiesGlobal cortical standardized uptake value ratioHead comparisonCortical standardized uptake value ratioRegional standardized uptake value ratiosAβ positron emission tomographyAmyloid-β positron emission tomographyAlzheimer's disease clinical trialsPET imagingUptake value ratioAβ PET imagingSimulated clinical trialTwo-sample t-testDrug armPittsburgh CompoundPET scansWelch two sample t-testReductions in synaptic marker SV2A in early-course Schizophrenia
Yoon J, Zhang Z, Mormino E, Davidzon G, Minzenberg M, Ballon J, Kalinowski A, Hardy K, Naganawa M, Carson R, Khalighi M, Park J, Levinson D, Chin F. Reductions in synaptic marker SV2A in early-course Schizophrenia. Journal Of Psychiatric Research 2023, 161: 213-217. PMID: 36934603, DOI: 10.1016/j.jpsychires.2023.02.026.Peer-Reviewed Original ResearchConceptsChronic patientsSynaptic pruningStage of illnessEarly course patientsEarly course schizophreniaSeverity of delusionsWidespread reductionMajor disease mechanismsSynaptic deficitsSynaptic markersSynaptic eliminationPET scansFormal onsetBrain regionsSignificant positive correlationPatientsSchizophrenia studiesSchizophreniaDisease mechanismsCognitive performanceIllnessEarly phaseSpecific bindingPresent studyPositive correlationIn Vivo Imaging and Kinetic Modeling of Novel Glycogen Synthase Kinase-3 Radiotracers [11C]OCM-44 and [18F]OCM-50 in Non-Human Primates
Smart K, Zheng M, Holden D, Felchner Z, Zhang L, Han Y, Ropchan J, Carson R, Vasdev N, Huang Y. In Vivo Imaging and Kinetic Modeling of Novel Glycogen Synthase Kinase-3 Radiotracers [11C]OCM-44 and [18F]OCM-50 in Non-Human Primates. Pharmaceuticals 2023, 16: 194. PMID: 37259346, PMCID: PMC9959234, DOI: 10.3390/ph16020194.Peer-Reviewed Original ResearchPositron emission tomographyNon-human primatesMetabolite-corrected arterial input functionML/Free fractionWarrants further evaluationPotential therapeutic targetGood brain uptakeAdult rhesus macaquesPlasma free fractionArterial blood samplingGray matter regionsTwo-tissue compartment modelBrain uptakeRegional time-activity curvesBlood samplingPsychiatric disordersPET scansTherapeutic targetTime-activity curvesGray matterBrain regionsEmission tomographyFurther evaluationArterial input function
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 modelsEvaluation of the α-synuclein PET radiotracer (d3)-[11C]MODAG-001 in pigs
Raval N, Madsen C, Shalgunov V, Nasser A, Battisti U, Beaman E, Juhl M, Jørgensen L, Herth M, Hansen H, Plavén-Sigray P, Knudsen G. Evaluation of the α-synuclein PET radiotracer (d3)-[11C]MODAG-001 in pigs. Nuclear Medicine And Biology 2022, 114: 42-48. PMID: 36095921, DOI: 10.1016/j.nucmedbio.2022.08.001.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseOccipital cortexΑ-synuclein pre-formed fibrilsInjected regionΑ-synuclein pathologyAD brain homogenatesDose-dependent effectPositron emission tomography (PET) radiotracerPre-formed fibrilsΑ-synuclein aggregatesReference regionAD homogenatesLogan graphical analysisLewy bodiesHistopathological hallmarksEarly diagnosisParkinson's diseasePET scansBrain homogenatesTime-activity curvesPig modelBrain regionsTomography radiotracerPig brainPET radiotracersAn in vivo Pig Model for Testing Novel Positron Emission Tomography Radioligands Targeting Cerebral Protein Aggregates
Raval NR, Nasser A, Madsen CA, Beschorner N, Beaman EE, Juhl M, Lehel S, Palner M, Svarer C, Plavén-Sigray P, Jørgensen LM, Knudsen GM. An in vivo Pig Model for Testing Novel Positron Emission Tomography Radioligands Targeting Cerebral Protein Aggregates. Frontiers In Neuroscience 2022, 16: 847074. PMID: 35368260, PMCID: PMC8966485, DOI: 10.3389/fnins.2022.847074.Peer-Reviewed Original ResearchPositron emission tomographyNovel radioligandPig modelAlzheimer's diseaseEmission tomographyΑ-synucleinGood translational modelΑ-synuclein pathologyBlood-brain barrierPostmortem human brain tissueReference tissue model 2Gadolinium-enhanced MRILarge animal modelNovel positron emission tomographyHuman brain tissueTimes higher uptakeCerebral injectionLewy bodiesVivo pig modelSaline injectionEssential clinical toolOccipital cortexParkinson's diseaseAppropriate radioligandsPET scans
2021
Brain target occupancy of LY3372689, an inhibitor of the O‐GlcNAcase (OGA) enzyme, following administration of single and multiple doses to healthy volunteers
Kielbasa W, Shcherbinin S, Goldsmith P, Phipps K, Biglan K, Mancini M, Russell D, Constantinescu C, Gunn R, Nuthall H, Mergott D, Lowe S, Collins E. Brain target occupancy of LY3372689, an inhibitor of the O‐GlcNAcase (OGA) enzyme, following administration of single and multiple doses to healthy volunteers. Alzheimer's & Dementia 2021, 17 DOI: 10.1002/alz.057774.Peer-Reviewed Original ResearchHealthy volunteersEnzyme occupancyPET scansSingle doseMultiple-dose clinical studiesPost-dose intervalPositron emission tomography radioligandBaseline PET scanLonger clinical trialsTarget occupancyTau-related diseasesMultiple dosesMultiple dosingClinical trialsPlasma pharmacokineticsClinical studiesEfficacy trialsSD studiesDose selectionTomography radioligandEnzyme inhibitorsPotential treatmentAlzheimer's diseasePET studiesTarget engagementPET Image Denoising Using a Deep-Learning Method for Extremely Obese Patients
Liu H, Yousefi H, Mirian N, Lin M, Menard D, Gregory M, Aboian M, Boustani A, Chen M, Saperstein L, Pucar D, Kulon M, Liu C. PET Image Denoising Using a Deep-Learning Method for Extremely Obese Patients. IEEE Transactions On Radiation And Plasma Medical Sciences 2021, 6: 766-770. PMID: 37284026, PMCID: PMC10241407, DOI: 10.1109/trpms.2021.3131999.Peer-Reviewed Original ResearchA metabolically stable PET tracer for imaging synaptic vesicle protein 2A: synthesis and preclinical characterization of [18F]SDM-16
Zheng C, Holden D, Zheng MQ, Pracitto R, Wilcox KC, Lindemann M, Felchner Z, Zhang L, Tong J, Fowles K, Finnema SJ, Nabulsi N, Carson RE, Huang Y, Cai Z. A metabolically stable PET tracer for imaging synaptic vesicle protein 2A: synthesis and preclinical characterization of [18F]SDM-16. European Journal Of Nuclear Medicine And Molecular Imaging 2021, 49: 1482-1496. PMID: 34761284, PMCID: PMC8940841, DOI: 10.1007/s00259-021-05597-5.Peer-Reviewed Original ResearchConceptsTest-retest variabilityVolume of distributionCentral nervous systemTime-activity curvesPET tracersCentrum semiovaleSynaptic vesicle protein 2AAbsolute test-retest variabilityWhole central nervous systemNonhuman primate brainPlasma free fractionBrain PET scansHigh specific bindingSpecific bindingNondisplaceable volumePlasma input functionNHP brainOne-tissue compartment modelArterial bloodRegional time-activity curvesPET scansNervous systemPrimate brainMonkey brainPreclinical characterization
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