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 ResearchMeSH KeywordsAnimalsBrainGlioblastomaPoly(ADP-ribose) Polymerase InhibitorsPositron-Emission TomographyPrimatesRatsTissue DistributionConceptsPositron 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
2022
Translational PET Imaging of Spinal Cord Injury with the Serotonin Transporter Tracer [11C]AFM
Fang H, Rossano S, Wang X, Nabulsi N, Kelley B, Fowles K, Ropchan J, Strittmatter SM, Carson RE, Huang Y. Translational PET Imaging of Spinal Cord Injury with the Serotonin Transporter Tracer [11C]AFM. Molecular Imaging And Biology 2022, 24: 560-569. PMID: 35020138, PMCID: PMC9550197, DOI: 10.1007/s11307-021-01698-7.Peer-Reviewed Original ResearchConceptsSpinal cord injurySpinal cordHealthy ratsHuman spinal cordCord injurySerotonin transporterRat modelRodent modelsPET imagingTranslational PET imagingSCI rat modelIntact spinal cordSpinal cord caudalRodent spinal cordSerotonin transporter tracerUse of PETCervical uptakeSERT changesSCI animalsSCI patientsPresynaptic serotonin transporterCord caudalAxon damageSerotonin systemSERT radioligand
2019
First in-human PET study and kinetic evaluation of [18F]AS2471907 for imaging 11β-hydroxysteroid dehydrogenase type 1
Bhatt S, Nabulsi NB, Li S, Cai Z, Matuskey D, Bini J, Najafzadeh S, Kapinos M, Ropchan JR, Carson RE, Cosgrove KP, Huang Y, Hillmer AT. First in-human PET study and kinetic evaluation of [18F]AS2471907 for imaging 11β-hydroxysteroid dehydrogenase type 1. Cerebrovascular And Brain Metabolism Reviews 2019, 40: 695-704. PMID: 30895878, PMCID: PMC7168798, DOI: 10.1177/0271678x19838633.Peer-Reviewed Original ResearchImaging the Enzyme 11β-Hydroxysteroid Dehydrogenase Type 1 with PET: Evaluation of the Novel Radiotracer 11C-AS2471907 in Human Brain
Gallezot JD, Nabulsi N, Henry S, Pracitto R, Planeta B, Ropchan J, Lin SF, Labaree D, Kapinos M, Shirali A, Lara-Jaime T, Gao H, Matuskey D, Walzer M, Marek GJ, Bellaire S, Yuan N, Carson RE, Huang Y. Imaging the Enzyme 11β-Hydroxysteroid Dehydrogenase Type 1 with PET: Evaluation of the Novel Radiotracer 11C-AS2471907 in Human Brain. Journal Of Nuclear Medicine 2019, 60: 1140-1146. PMID: 30877174, DOI: 10.2967/jnumed.118.219766.Peer-Reviewed Original ResearchConceptsTest-retest variabilityNondisplaceable distribution volumeOccipital cortexEnzyme 11β-hydroxysteroid dehydrogenase type 1White matterDistribution volumeTreatment of depressionDehydrogenase type 1Large cortical regionsPosttraumatic stress disorderHuman brainAdditional scansIntraclass correlation coefficientAge-related cognitive functionBolus administrationFrontal cortexCaudate nucleusAdipose tissueTime-activity curvesNovel radiotracersGlucocorticoid levelsParietal cortexCortical regionsPattern of uptakeType 1Evaluation 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
2017
Evaluation of the Lysophosphatidic Acid Receptor Type 1 Radioligand 11C-BMT-136088 for Lung Imaging in Rhesus Monkeys
Gallezot JD, Nabulsi NB, Holden D, Lin SF, Labaree D, Ropchan J, Najafzadeh S, Donnelly DJ, Cao K, Bonacorsi S, Seiders J, Roppe J, Hayes W, Huang Y, Du S, Carson RE. Evaluation of the Lysophosphatidic Acid Receptor Type 1 Radioligand 11C-BMT-136088 for Lung Imaging in Rhesus Monkeys. Journal Of Nuclear Medicine 2017, 59: 327-333. PMID: 28864634, DOI: 10.2967/jnumed.117.195073.Peer-Reviewed Original ResearchConceptsMultilinear analysis 1Rhesus monkeysHighest organ doseLung tissue injuryLung regionsΜSv/MBqPlasma free fractionReceptor type 1Test-retest scansTest-retest variabilityVivo dissociationMolecule lysophosphatidic acidRight lung regionsML of plasmaNondisplaceable volumePulmonary fibrosisLung fibrosisVascular leakageInfusion protocolPlasma concentrationsTissue injuryDrug doseNormal healingOrgan doseType 1Kinetic evaluation and test–retest reproducibility of [11C]UCB-J, a novel radioligand for positron emission tomography imaging of synaptic vesicle glycoprotein 2A in humans
Finnema SJ, Nabulsi NB, Mercier J, Lin SF, Chen MK, Matuskey D, Gallezot JD, Henry S, Hannestad J, Huang Y, Carson RE. Kinetic evaluation and test–retest reproducibility of [11C]UCB-J, a novel radioligand for positron emission tomography imaging of synaptic vesicle glycoprotein 2A in humans. Cerebrovascular And Brain Metabolism Reviews 2017, 38: 2041-2052. PMID: 28792356, PMCID: PMC6259313, DOI: 10.1177/0271678x17724947.Peer-Reviewed Original ResearchA multi species evaluation of the radiation dosimetry of [11C]erlotinib, the radiolabeled analog of a clinically utilized tyrosine kinase inhibitor
Petrulli JR, Hansen SB, Abourbeh G, Yaqub M, Bahce I, Holden D, Huang Y, Nabulsi NB, Contessa JN, Mishani E, Lammertsma AA, Morris ED. A multi species evaluation of the radiation dosimetry of [11C]erlotinib, the radiolabeled analog of a clinically utilized tyrosine kinase inhibitor. Nuclear Medicine And Biology 2017, 47: 56-61. PMID: 28126682, PMCID: PMC5360653, DOI: 10.1016/j.nucmedbio.2016.12.009.Peer-Reviewed Original ResearchConceptsTyrosine kinase inhibitorsTime-activity curvesEquivalent doseNon-small cell lung cancer patientsStage IIIA NSCLC patientsEpidermal growth factor receptor (EGFR) mutationsCell lung cancer patientsCritical organsKinase inhibitorsIIIA NSCLC patientsLung cancer patientsHighest equivalent doseTime-integrated activity coefficientsWhole bodyMean equivalent dosesRhesus macaque monkeysNSCLC patientsDosimetry profileCancer patientsGallbladder wallReceptor mutationsMacaque monkeysIdentifiable organsInjected activityEffective dose
2016
Imaging of cerebral α4β2* nicotinic acetylcholine receptors with (−)-[18F]Flubatine PET: Implementation of bolus plus constant infusion and sensitivity to acetylcholine in human brain
Hillmer AT, Esterlis I, Gallezot JD, Bois F, Zheng MQ, Nabulsi N, Lin SF, Papke RL, Huang Y, Sabri O, Carson RE, Cosgrove KP. Imaging of cerebral α4β2* nicotinic acetylcholine receptors with (−)-[18F]Flubatine PET: Implementation of bolus plus constant infusion and sensitivity to acetylcholine in human brain. NeuroImage 2016, 141: 71-80. PMID: 27426839, PMCID: PMC5026941, DOI: 10.1016/j.neuroimage.2016.07.026.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAdultBenzamidesBrainBridged Bicyclo Compounds, HeterocyclicComputer SimulationHumansImage Interpretation, Computer-AssistedInfusions, IntraventricularMetabolic Clearance RateMiddle AgedModels, NeurologicalMolecular ImagingNeurotransmitter AgentsPositron-Emission TomographyRadiopharmaceuticalsReceptors, NicotinicReproducibility of ResultsSensitivity and SpecificityTissue DistributionYoung AdultConceptsGray matter regionsPreclinical Evaluation of 18F-PF-05270430, a Novel PET Radioligand for the Phosphodiesterase 2A Enzyme
Chen L, Nabulsi N, Naganawa M, Zasadny K, Skaddan MB, Zhang L, Najafzadeh S, Lin SF, Helal CJ, Boyden TL, Chang C, Ropchan J, Carson RE, Villalobos A, Huang Y. Preclinical Evaluation of 18F-PF-05270430, a Novel PET Radioligand for the Phosphodiesterase 2A Enzyme. Journal Of Nuclear Medicine 2016, 57: 1448-1453. PMID: 27199356, PMCID: PMC5093921, DOI: 10.2967/jnumed.115.171454.Peer-Reviewed Original ResearchAnimalsAzabicyclo CompoundsAzetidinesBrainCyclic Nucleotide Phosphodiesterases, Type 2Macaca mulattaMaleMetabolic Clearance RateMolecular ImagingOrgan SpecificityPositron-Emission TomographyRadiopharmaceuticalsRatsRats, Sprague-DawleyReproducibility of ResultsSensitivity and SpecificitySpecies SpecificityTissue DistributionFirst-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
2014
Evaluation of 11C-BU99008, a PET Ligand for the Imidazoline2 Binding Sites in Rhesus Brain
Parker CA, Nabulsi N, Holden D, Lin SF, Cass T, Labaree D, Kealey S, Gee AD, Husbands SM, Quelch D, Carson RE, Nutt DJ, Huang Y, Tyacke RJ. Evaluation of 11C-BU99008, a PET Ligand for the Imidazoline2 Binding Sites in Rhesus Brain. Journal Of Nuclear Medicine 2014, 55: 838-844. PMID: 24711648, DOI: 10.2967/jnumed.113.131854.Peer-Reviewed Original ResearchPhosphodiesterase 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
2013
Decreased norepinephrine transporter availability in obesity: Positron Emission Tomography imaging with (S,S)-[11C]O-methylreboxetine
Li CS, Potenza MN, Lee DE, Planeta B, Gallezot JD, Labaree D, Henry S, Nabulsi N, Sinha R, Ding YS, Carson RE, Neumeister A. Decreased norepinephrine transporter availability in obesity: Positron Emission Tomography imaging with (S,S)-[11C]O-methylreboxetine. NeuroImage 2013, 86: 306-310. PMID: 24121204, PMCID: PMC3947246, DOI: 10.1016/j.neuroimage.2013.10.004.Peer-Reviewed Original ResearchConceptsBody mass indexMultilinear reference tissue model 2Norepinephrine transporterNoradrenergic dysfunctionObese individualsLean individualsStructural MR scansBPND valuesNorepinephrine transporter availabilityReference tissue model 2Positron emission tomography (PET) imagingEmission Tomography ImagingPositron emission tomographyBrain norepinephrine transportersNE clearanceMass indexRaphe nucleusLocus coeruleusSynaptic availabilityObese peopleTransporter availabilityOccipital cortexComparison subjectsHealthy individualsObesityClinical doses of atomoxetine significantly occupy both norepinephrine and serotonin transports: Implications on treatment of depression and ADHD
Ding YS, Naganawa M, Gallezot JD, Nabulsi N, Lin SF, Ropchan J, Weinzimmer D, McCarthy TJ, Carson RE, Huang Y, Laruelle M. Clinical doses of atomoxetine significantly occupy both norepinephrine and serotonin transports: Implications on treatment of depression and ADHD. NeuroImage 2013, 86: 164-171. PMID: 23933039, DOI: 10.1016/j.neuroimage.2013.08.001.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic Uptake InhibitorsAnimalsAtomoxetine HydrochlorideAttention Deficit Disorder with HyperactivityBrainDepressionDose-Response Relationship, DrugMacaca mulattaNorepinephrine Plasma Membrane Transport ProteinsPositron-Emission TomographyPropylaminesSerotonin Plasma Membrane Transport ProteinsTissue DistributionConceptsTreatment of depressionNorepinephrine transporterComparative PET imaging studyMetabolite-corrected arterial input functionFinal infusion rateDoses of atomoxetineDose-dependent occupancyPET imaging studiesSelective serotonin transporter (SERT) ligandNon-human primatesPlasma levelsSelective blockadeSaline infusionClinical dosesTherapeutic effectInfusion rateRelevant dosePET scansAtomoxetineRelevant dosesSerotonin transporter ligandDistribution volumeImaging studiesRhesus monkeysArterial input functionDetermination of the In Vivo Selectivity of a New κ-Opioid Receptor Antagonist PET Tracer 11C-LY2795050 in the Rhesus Monkey
Kim SJ, Zheng MQ, Nabulsi N, Labaree D, Ropchan J, Najafzadeh S, Carson RE, Huang Y, Morris ED. Determination of the In Vivo Selectivity of a New κ-Opioid Receptor Antagonist PET Tracer 11C-LY2795050 in the Rhesus Monkey. Journal Of Nuclear Medicine 2013, 54: 1668-1674. PMID: 23918735, PMCID: PMC5824998, DOI: 10.2967/jnumed.112.118877.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzamidesBrainComputer SimulationImage Interpretation, Computer-AssistedMacaca mulattaMetabolic Clearance RateModels, BiologicalPositron-Emission TomographyPyrrolidinesRadiopharmaceuticalsReceptors, Opioid, kappaReproducibility of ResultsSensitivity and SpecificityTissue DistributionStudies of the metabotropic glutamate receptor 5 radioligand [11C]ABP688 with N‐acetylcysteine challenge in rhesus monkeys
Sandiego CM, Nabulsi N, Lin S, Labaree D, Najafzadeh S, Huang Y, Cosgrove K, Carson RE. Studies of the metabotropic glutamate receptor 5 radioligand [11C]ABP688 with N‐acetylcysteine challenge in rhesus monkeys. Synapse 2013, 67: 489-501. PMID: 23424090, PMCID: PMC3710146, DOI: 10.1002/syn.21656.Peer-Reviewed Original ResearchConceptsN-acetylcysteineRhesus monkeysCerebellum gray matterMetabotropic glutamate receptor 5N-acetylcysteine challengeBaboon studiesGlutamate receptor 5Non-displaceable binding potentialHigh intersubject variabilityReference regionRecent pilot studySignificant global decreaseGlutamate transmissionNAC doseEndogenous glutamatePsychiatric illnessReceptor 5Gray matterAllosteric antagonistsPilot studyReceptor bindingIntersubject variabilitySame dayDoseMonkeys
2010
Evaluation of [11C]MRB for assessment of occupancy of norepinephrine transporters: Studies with atomoxetine in non-human primates
Gallezot JD, Weinzimmer D, Nabulsi N, Lin SF, Fowles K, Sandiego C, McCarthy TJ, Maguire RP, Carson RE, Ding YS. Evaluation of [11C]MRB for assessment of occupancy of norepinephrine transporters: Studies with atomoxetine in non-human primates. NeuroImage 2010, 56: 268-279. PMID: 20869448, PMCID: PMC3710586, DOI: 10.1016/j.neuroimage.2010.09.040.Peer-Reviewed Original ResearchConceptsAttention deficit hyperactivity disorderPositron emission tomographyNorepinephrine transporterDrug occupancy studiesRhesus monkeysReference regionTreatment of depressionDose-dependent reductionVolume of distributionArterial blood samplingSuitable reference regionOccupancy studiesNon-human primatesBrain norepinephrine transportersPromising radioligandPlasma levelsTherapeutic doseOccipital cortexBlood samplingUptake inhibitorAtomoxetineEmission tomographyEffective dosePET studiesArterial input function