2024
Synaptic loss and its association with symptom severity in Parkinson’s disease
Holmes S, Honhar P, Tinaz S, Naganawa M, Hilmer A, Gallezot J, Dias M, Yang Y, Toyonaga T, Esterlis I, Mecca A, Van Dyck C, Henry S, Ropchan J, Nabulsi N, Louis E, Comley R, Finnema S, Carson R, Matuskey D. Synaptic loss and its association with symptom severity in Parkinson’s disease. Npj Parkinson's Disease 2024, 10: 42. PMID: 38402233, PMCID: PMC10894197, DOI: 10.1038/s41531-024-00655-9.Peer-Reviewed Original ResearchSynaptic density lossPositron emission tomographyBinds to synaptic vesicle glycoprotein 2AAssociated with symptom severityParkinson's diseaseHigh-resolution positron emission tomographySynaptic vesicle glycoprotein 2ADuration of illnessPositron emission tomography scanBrain perfusionIllness durationSymptom severitySeverity of symptomsHC groupSubstantia nigraSynaptic densityLiving brainPD individualsClinical insightsDensity lossPD patientsEmission tomographyBrainSynaptic lossSynapse loss
2022
Drug characteristics derived from kinetic modeling: combined 11C-UCB-J human PET imaging with levetiracetam and brivaracetam occupancy of SV2A
Naganawa M, Gallezot J, Finnema S, Maguire R, Mercier J, Nabulsi N, Kervyn S, Henry S, Nicolas J, Huang Y, Chen M, Hannestad J, Klitgaard H, Stockis A, Carson R. Drug characteristics derived from kinetic modeling: combined 11C-UCB-J human PET imaging with levetiracetam and brivaracetam occupancy of SV2A. EJNMMI Research 2022, 12: 71. PMID: 36346513, PMCID: PMC9643320, DOI: 10.1186/s13550-022-00944-5.Peer-Reviewed Original ResearchTime-activity curvesBrain entryDrug concentrationsNon-human primate brainAnti-seizure activitySynaptic vesicle glycoprotein 2APlasma drug concentrationsPrevious human studiesBackgroundAntiepileptic drugsHealthy subjectsBlood samplesHuman studiesLevetiracetamPrimate brainEmission tomography dataBrivaracetamDistribution volumeArterial input functionBrainDrug characteristicsPositron emission tomography dataDrug entryFree fractionDrugsKinetic parameters k1
2021
PET Imaging Estimates of Regional Acetylcholine Concentration Variation in Living Human Brain
Smart K, Naganawa M, Baldassarri SR, Nabulsi N, Ropchan J, Najafzadeh S, Gao H, Navarro A, Barth V, Esterlis I, Cosgrove KP, Huang Y, Carson RE, Hillmer AT. PET Imaging Estimates of Regional Acetylcholine Concentration Variation in Living Human Brain. Cerebral Cortex 2021, 31: 2787-2798. PMID: 33442731, PMCID: PMC8355478, DOI: 10.1093/cercor/bhaa387.Peer-Reviewed Original ResearchConceptsACh concentrationHuman volunteersHigh ACh concentrationsMuscarinic antagonist scopolamineHealthy human volunteersHuman brainCholinergic receptorsNicotine challengeAntagonist scopolaminePreclinical studiesStriatal regionsPET scansEndogenous neurotransmittersNeuropsychiatric diseasesNonhuman primatesWhole-brain imagesDrug occupancyNicotinic ligandsClinical populationsBrainAcetylcholineDistinct functional rolesStriatumVolunteersFunctional role
2020
Tobacco Smoking in People Is Not Associated with Altered 18-kDa Translocator Protein Levels: A PET Study
Hillmer AT, Matuskey D, Huang Y, Nabulsi N, Ropchan J, Carson RE, O'Malley SS, Cosgrove KP. Tobacco Smoking in People Is Not Associated with Altered 18-kDa Translocator Protein Levels: A PET Study. Journal Of Nuclear Medicine 2020, 61: 1200-1204. PMID: 32005773, PMCID: PMC7413239, DOI: 10.2967/jnumed.119.237735.Peer-Reviewed Original ResearchConceptsTobacco smokingTobacco smokersTSPO levelsImmune systemPET studiesBrain immune systemBrain TSPO levelsPrimary immunocompetent cellsPrevious PET studiesTranslocator proteinTranslocator protein (TSPO) levelsInflammatory effectsImmunocompetent cellsArterial bloodTobacco smokePET scansNonsmokersSmokersRadiotracer concentrationMedium effect sizeSmokingPET imagingBrainProtein levelsSignificant differences
2017
Evaluation of (‐)‐[18F]Flubatine‐specific binding: Implications for reference region approaches
Bhatt S, Hillmer AT, Nabulsi N, Matuskey D, Lim K, Lin S, Esterlis I, Carson RE, Huang Y, Cosgrove KP. Evaluation of (‐)‐[18F]Flubatine‐specific binding: Implications for reference region approaches. Synapse 2017, 72 PMID: 29105121, PMCID: PMC6547815, DOI: 10.1002/syn.22016.Peer-Reviewed Original ResearchConceptsNicotinic acetylcholine receptorsPositron emission tomographyCorpus callosumAcetylcholine receptorsGreater receptor occupancyReference regionRegion-based quantificationMin bolusTobacco smokersFrontal cortexTobacco cigarettesReceptor occupancyConstant infusionDistribution volumeEmission tomographyCallosumSpecific bindingBrainReceptorsSmokersSmokingPutamenInfusionBolusCortexMicroglial depletion and activation: A [11C]PBR28 PET study in nonhuman primates
Hillmer AT, Holden D, Fowles K, Nabulsi N, West BL, Carson RE, Cosgrove KP. Microglial depletion and activation: A [11C]PBR28 PET study in nonhuman primates. EJNMMI Research 2017, 7: 59. PMID: 28741281, PMCID: PMC5524658, DOI: 10.1186/s13550-017-0305-0.Peer-Reviewed Original ResearchBrain microgliaTranslocator proteinAcute lipopolysaccharide administrationArterial blood samplingPositron emission tomography (PET) imagingReceptor kinase inhibitorMicroglia changesLipopolysaccharide administrationNeuroimmune functionMicroglial depletionMicroglia dynamicsTSPO levelsBlood samplingPET studiesOne animalKinase inhibitorsTomography imagingBaselineConclusionsThese studiesBrainMicrogliaImaging paradigmMacaca mulattaPreliminary evidenceImportant target
2016
Synthesis and Preclinical Evaluation of 11C-UCB-J as a PET Tracer for Imaging the Synaptic Vesicle Glycoprotein 2A in the Brain
Nabulsi N, Mercier J, Holden D, Carré S, Najafzadeh S, Vandergeten MC, Lin SF, Deo A, Price N, Wood M, Lara-Jaime T, Montel F, Laruelle M, Carson RE, Hannestad J, Huang Y. Synthesis and Preclinical Evaluation of 11C-UCB-J as a PET Tracer for Imaging the Synaptic Vesicle Glycoprotein 2A in the Brain. Journal Of Nuclear Medicine 2016, 57: 777-784. PMID: 26848175, DOI: 10.2967/jnumed.115.168179.Peer-Reviewed Original ResearchConceptsSynaptic vesicle glycoprotein 2AWhole-body biodistributionPET radiotracersNonhuman primatesDose-limiting organHigher free fractionGray matter regionsBaseline VTNondisplaceable distribution volumeAntiepileptic drugsVitro inhibition constantSynaptic densityPreclinical evaluationMonkey brainDistribution volumeArterial samplingEndocrine cellsRegional volumesMatter regionsRhesus macaquesPET tracersUCBFree fractionBrainTarget occupancy
2014
Phosphodiesterase 10A PET Radioligand Development Program: From Pig to Human
Plisson C, Weinzimmer D, Jakobsen S, Natesan S, Salinas C, Lin SF, Labaree D, Zheng MQ, Nabulsi N, Marques TR, Kapur S, Kawanishi E, Saijo T, Gunn RN, Carson RE, Rabiner EA. Phosphodiesterase 10A PET Radioligand Development Program: From Pig to Human. Journal Of Nuclear Medicine 2014, 55: 595-601. PMID: 24614221, DOI: 10.2967/jnumed.113.131409.Peer-Reviewed Original ResearchConceptsMP-10Primate brainRadioligand candidatesBaseline PET studyFirst human administrationTissue kineticsNonhuman primate brainRegional binding potentialSelective PDE10A inhibitorDose-dependent mannerOutcome measuresPreclinical studiesBrain regionsFurther evaluationPET studiesPig brainPET tracersPDE10A inhibitorsBrainVivo studiesReference tissueHuman administrationHuman brainAdministrationGood radiochemical yield
2012
Affinity and selectivity of [11C]‐(+)‐PHNO for the D3 and D2 receptors in the rhesus monkey brain in vivo
Gallezot J, Beaver JD, Gunn RN, Nabulsi N, Weinzimmer D, Singhal T, Slifstein M, Fowles K, Ding Y, Huang Y, Laruelle M, Carson RE, Rabiner EA. Affinity and selectivity of [11C]‐(+)‐PHNO for the D3 and D2 receptors in the rhesus monkey brain in vivo. Synapse 2012, 66: 489-500. PMID: 22213512, DOI: 10.1002/syn.21535.Peer-Reviewed Original ResearchConceptsHuman positron emission tomography studiesPositron emission tomography studyRhesus monkey brainEmission tomography studiesDopamine D2 receptorsRegional binding potentialDopamine D3 receptorAnesthetized primatePHNO signalFuture PET studiesInfusion paradigmD2 receptorsMonkey brainPrimate brainVivo affinityRhesus monkeysPET studiesTomography studyD2RPHNOBrainReceptorsD3RRegional fractionHuman brain
2011
Assessing the sensitivity of [11C]p943, a novel 5‐HTIB radioligand, to endogenous serotonin release
Cosgrove KP, Kloczynski T, Nabulsi N, Weinzimmer D, Lin S, Staley JK, Bhagwagar Z, Carson RE. Assessing the sensitivity of [11C]p943, a novel 5‐HTIB radioligand, to endogenous serotonin release. Synapse 2011, 65: 1113-1117. PMID: 21484884, PMCID: PMC3149753, DOI: 10.1002/syn.20942.Peer-Reviewed Original ResearchConceptsFenfluramine-induced changesReceptor occupancyDoses of fenfluraminePositron emission tomography radioligandEndogenous serotonin releaseNonhuman primate brainSerotonin releaseLow doseHigh doseTomography radioligandPrimate brainRhesus monkeysFenfluramineRhesus macaquesPET imagingHuman brainBaboonsDoseDosesRadioligandBrainCurrent studyReceptors