2023
Preclinical evaluation of a brain penetrant PARP PET imaging probe in rat glioblastoma and nonhuman primates
Chen B, Ojha D, Toyonaga T, Tong J, Pracitto R, Thomas M, Liu M, Kapinos M, Zhang L, Zheng M, Holden D, Fowles K, Ropchan J, Nabulsi N, De Feyter H, Carson R, Huang Y, Cai Z. Preclinical evaluation of a brain penetrant PARP PET imaging probe in rat glioblastoma and nonhuman primates. European Journal Of Nuclear Medicine And Molecular Imaging 2023, 50: 2081-2099. PMID: 36849748, DOI: 10.1007/s00259-023-06162-y.Peer-Reviewed Original ResearchConceptsPositron emission tomographyHealthy nonhuman primatesVolume of distributionDistribution volume ratioBrain kineticsRat glioblastoma modelPreclinical evaluationBrain regionsGlioblastoma modelPET tracersNonhuman primatesTumor-bearing ratsEx vivo biodistributionPET imaging resultsActive clinical trialsTreatment of glioblastomaHigh specific uptakeDynamic PET scansNoninvasive quantificationBrain positron emission tomographyNondisplaceable volumeBrain penetrationLow nonspecific uptakePrognostic informationClinical trials
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 roleAssessment of test-retest reproducibility of [18F]SynVesT-1, a novel radiotracer for PET imaging of synaptic vesicle glycoprotein 2A
Li S, Naganawa M, Pracitto R, Najafzadeh S, Holden D, Henry S, Matuskey D, Emery PR, Cai Z, Ropchan J, Nabulsi N, Carson RE, Huang Y. Assessment of test-retest reproducibility of [18F]SynVesT-1, a novel radiotracer for PET imaging of synaptic vesicle glycoprotein 2A. European Journal Of Nuclear Medicine And Molecular Imaging 2021, 48: 1327-1338. PMID: 33416954, DOI: 10.1007/s00259-020-05149-3.Peer-Reviewed Original ResearchConceptsTest-retest reproducibilityTime-activity curvesBPND valuesNonhuman primatesAbsolute test-retest variabilitySynaptic vesicle glycoprotein 2AHigh brain uptakeNon-displaceable binding potentialExcellent test-retest reproducibilityGray matter areasHealthy human subjectsHigh uptakeTest-retest variabilityDynamic PET scanningTest-retest reliabilityBrain uptakeDistribution volume valuesCentrum semiovaleUrinary bladderOne-tissue compartment modelMaximum SUVPET scanningPET scansTracer uptakeBrain disorders
2020
First-in-Human Evaluation of 18F-SynVesT-1, a Radioligand for PET Imaging of Synaptic Vesicle Glycoprotein 2A
Naganawa M, Li S, Nabulsi N, Henry S, Zheng MQ, Pracitto R, Cai Z, Gao H, Kapinos M, Labaree D, Matuskey D, Huang Y, Carson RE. First-in-Human Evaluation of 18F-SynVesT-1, a Radioligand for PET Imaging of Synaptic Vesicle Glycoprotein 2A. Journal Of Nuclear Medicine 2020, 62: 561-567. PMID: 32859701, PMCID: PMC8049363, DOI: 10.2967/jnumed.120.249144.Peer-Reviewed Original ResearchConceptsC-UCBSynaptic densityRegional time-activity curvesTime-activity curvesDistribution volumeMetabolite-corrected arterial input functionPET imagingMultilinear analysis 1Synaptic vesicle glycoprotein 2AAntiepileptic drug levetiracetamTotal distribution volumeNondisplaceable distribution volumeCentrum semiovaleBlocking doseHealthy volunteersHuman studiesDrug levetiracetamLassen plotNeuropsychiatric disordersPET radioligandArterial input functionNonhuman primatesLevetiracetamReference regionRadioligand
2019
Synthesis and in vivo evaluation of [18F]UCB-J for PET imaging of synaptic vesicle glycoprotein 2A (SV2A)
Li S, Cai Z, Zhang W, Holden D, Lin SF, Finnema SJ, Shirali A, Ropchan J, Carre S, Mercier J, Carson RE, Nabulsi N, Huang Y. Synthesis and in vivo evaluation of [18F]UCB-J for PET imaging of synaptic vesicle glycoprotein 2A (SV2A). European Journal Of Nuclear Medicine And Molecular Imaging 2019, 46: 1952-1965. PMID: 31175396, PMCID: PMC6810698, DOI: 10.1007/s00259-019-04357-w.Peer-Reviewed Original ResearchConceptsSynaptic vesicle glycoprotein 2AHigh specific binding signalsNonhuman primatesPET imagingHigh brain uptakeRegional distribution volumesBrain uptakeSynaptic densityOne-tissue compartment modelExcellent imaging agentRegional time-activity curvesVivo biomarkersArterial samplesSpecific binding signalsPsychiatric diseasesTime-activity curvesAlzheimer's diseaseDistribution volumeNeuropsychiatric disordersRadioactive metabolitesRhesus monkeysPET radiotracersVivo evaluationDiseaseImaging agentEvaluation of 11C-LSN3172176 as a Novel PET Tracer for Imaging M1 Muscarinic Acetylcholine Receptors in Nonhuman Primates
Nabulsi NB, Holden D, Zheng MQ, Bois F, Lin SF, Najafzadeh S, Gao H, Ropchan J, Lara-Jaime T, Labaree D, Shirali A, Slieker L, Jesudason C, Barth V, Navarro A, Kant N, Carson RE, Huang Y. Evaluation of 11C-LSN3172176 as a Novel PET Tracer for Imaging M1 Muscarinic Acetylcholine Receptors in Nonhuman Primates. Journal Of Nuclear Medicine 2019, 60: 1147-1153. PMID: 30733324, DOI: 10.2967/jnumed.118.222034.Peer-Reviewed Original ResearchConceptsMuscarinic acetylcholine receptorsAcetylcholine receptorsNonhuman primatesM1 muscarinic acetylcholine receptorBrain time-activity curvesRich brain regionsArterial blood samplingNovel PET tracersSuitable reference regionRegional distribution volumesReference regionDevelopment of drugsBrain uptakeGlobus pallidusDistribution volume valuesNucleus accumbensBlood samplingPET scansTime-activity curvesCognitive impairmentAlzheimer's diseaseBrain regionsDistribution volumeSelective radiotracerRhesus monkeys
2018
Synthesis and in Vivo Evaluation of a Novel PET Radiotracer for Imaging of Synaptic Vesicle Glycoprotein 2A (SV2A) in Nonhuman Primates
Li S, Cai Z, Wu X, Holden D, Pracitto R, Kapinos M, Gao H, Labaree D, Nabulsi N, Carson RE, Huang Y. Synthesis and in Vivo Evaluation of a Novel PET Radiotracer for Imaging of Synaptic Vesicle Glycoprotein 2A (SV2A) in Nonhuman Primates. ACS Chemical Neuroscience 2018, 10: 1544-1554. PMID: 30396272, PMCID: PMC6810685, DOI: 10.1021/acschemneuro.8b00526.Peer-Reviewed Original ResearchConceptsSynaptic vesicle glycoprotein 2AStandardized uptake valuePET radiotracersNonhuman primatesAlterations of synapsesC-UCBPeak standardized uptake valueVivo evaluationHigh brain uptakeNovel PET radiotracersBrain uptakeSynaptic densityExcellent radiotracerPsychiatric disordersUptake valueCingulate cortexAlzheimer's diseaseBrain disordersNovel radiotracersRhesus monkeysNeurodegenerative diseasesTissue kineticsDiseaseAttractive imaging propertiesLevetiracetam
2017
The Search for a Subtype-Selective PET Imaging Agent for the GABAA Receptor Complex: Evaluation of the Radiotracer [11C]ADO in Nonhuman Primates
Lin SF, Bois F, Holden D, Nabulsi N, Pracitto R, Gao H, Kapinos M, Teng JK, Shirali A, Ropchan J, Carson RE, Elmore CS, Vasdev N, Huang Y. The Search for a Subtype-Selective PET Imaging Agent for the GABAA Receptor Complex: Evaluation of the Radiotracer [11C]ADO in Nonhuman Primates. Molecular Imaging 2017, 16: 1536012117731258. PMID: 28929924, PMCID: PMC5912275, DOI: 10.1177/1536012117731258.Peer-Reviewed Original ResearchConceptsNonhuman primatesNovel positron emission tomography (PET) radiotracerAbsolute test-retest variabilityFast tissue kineticsSubtype-selective GABATissue kineticsHigh brain uptakeGABAA receptor complexRegional binding potentialPositron emission tomography (PET) radiotracerPET imaging agentRegional distribution volumesTest-retest variabilityNondisplaceable volumeUndesirable side effectsRegion-specific distributionΓ-amino butyric acidAnticonvulsive effectBrain uptakeAnxiolytic effectsMinutes postinjectionOne-tissue compartment modelGABA sitesStriatal regionsRegional time-activity curves
2016
Quantitative projection of human brain penetration of the H3 antagonist PF-03654746 by integrating rat-derived brain partitioning and PET receptor occupancy
Sawant-Basak A, Chen L, Shaffer CL, Palumbo D, Schmidt A, Tseng E, Spracklin DK, Gallezot JD, Labaree D, Nabulsi N, Huang Y, Carson RE, McCarthy T. Quantitative projection of human brain penetration of the H3 antagonist PF-03654746 by integrating rat-derived brain partitioning and PET receptor occupancy. Xenobiotica 2016, 47: 119-126. PMID: 27353353, DOI: 10.3109/00498254.2016.1166531.Peer-Reviewed Original ResearchFirst-in-Human Assessment of the Novel PDE2A PET Radiotracer 18F-PF-05270430
Naganawa M, Waterhouse RN, Nabulsi N, Lin SF, Labaree D, Ropchan J, Tarabar S, DeMartinis N, Ogden A, Banerjee A, Huang Y, Carson RE. First-in-Human Assessment of the Novel PDE2A PET Radiotracer 18F-PF-05270430. Journal Of Nuclear Medicine 2016, 57: 1388-1395. PMID: 27103022, PMCID: PMC5093918, DOI: 10.2967/jnumed.115.166850.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAzabicyclo CompoundsAzetidinesBrainComputer SimulationCyclic Nucleotide Phosphodiesterases, Type 2Feasibility StudiesFemaleHumansIsotope LabelingMacaca mulattaMaleMetabolic Clearance RateModels, BiologicalMolecular ImagingOrgan SpecificityPilot ProjectsPositron-Emission TomographyRadiopharmaceuticalsReproducibility of ResultsSensitivity and SpecificityTissue DistributionConceptsTest-retest variabilityHuman studiesPET ligandWhite matterNeocortical regionsMultilinear analysis 1MSv/MBqHealthy male subjectsDetectable pharmacologic effectsAppropriate tracer kinetic modelsTest-retest protocolAdverse eventsBrain uptakePharmacologic effectsRegional time-activity curvesTarget doseTime-activity curvesTracer uptakeMale subjectsWhole brainBrain regionsEffective doseCritical organsPET radiotracersNonhuman primatesSynthesis 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