2022
Age, gender and body-mass-index relationships with in vivo CB1 receptor availability in healthy humans measured with [11C]OMAR PET
Radhakrishnan R, Worhunsky PD, Zheng MQ, Najafzadeh S, Gallezot JD, Planeta B, Henry S, Nabulsi N, Ranganathan M, Skosnik PD, Pittman B, Cyril D'Souza D, Carson RE, Huang Y, Potenza MN, Matuskey D. Age, gender and body-mass-index relationships with in vivo CB1 receptor availability in healthy humans measured with [11C]OMAR PET. NeuroImage 2022, 264: 119674. PMID: 36243269, DOI: 10.1016/j.neuroimage.2022.119674.Peer-Reviewed Original ResearchSystemic inflammation enhances stimulant-induced striatal dopamine elevation in tobacco smokers
Zakiniaeiz Y, Hoye J, Ryan Petrulli J, LeVasseur B, Stanley G, Gao H, Najafzadeh S, Ropchan J, Nabulsi N, Huang Y, Chen MK, Matuskey D, Barron DS, Kelmendi B, Fulbright RK, Hampson M, Cosgrove KP, Morris ED. Systemic inflammation enhances stimulant-induced striatal dopamine elevation in tobacco smokers. Brain Behavior And Immunity 2022, 106: 262-269. PMID: 36058419, PMCID: PMC10097458, DOI: 10.1016/j.bbi.2022.08.016.Peer-Reviewed Original ResearchConceptsEffects of LPSDopamine elevationTobacco smokersHealthy controlsSystemic inflammationDopamine systemImmune-brain interactionReward-related brain regionsAdministration of placeboAdministration of LPSSmoking statusRepeated-measures ANOVAPathophysiology of addictionDrug dosingPlaceboIndependent cohortSmokersDrug reinforcementEffect size determinationImmune systemRandomized orderBrain regionsLPSMethylphenidatePBO conditionNicotine Patch Alters Patterns of Cigarette Smoking-Induced Dopamine Release: Patterns Relate to Biomarkers Associated With Treatment Response
Zakiniaeiz Y, Liu H, Gao H, Najafzadeh S, Ropchan J, Nabulsi N, Huang Y, Matuskey D, Chen MK, Cosgrove KP, Morris ED. Nicotine Patch Alters Patterns of Cigarette Smoking-Induced Dopamine Release: Patterns Relate to Biomarkers Associated With Treatment Response. Nicotine & Tobacco Research 2022, 24: 1597-1606. PMID: 35100429, PMCID: PMC9575980, DOI: 10.1093/ntr/ntac026.Peer-Reviewed Original ResearchConceptsNicotine replacement therapyDopamine releasePlacebo patchDorsal striatumTobacco smokingReplacement therapyFirst-line pharmacological treatmentVentral striatumMajor public health burdenPositron emission tomography scanEmission tomography scanPublic health burdenNicotine dependence levelNicotine metabolism rateNicotinic acetylcholine receptorsCounter-balanced orderTobacco smokersCigarette smokingSmoking cessationDopamine terminalsPharmacological treatmentDependent smokersFast metabolizersSlow metabolizersNicotine acts
2021
Imaging brain cortisol regulation in PTSD with a target for 11β-hydroxysteroid dehydrogenase type 1
Bhatt S, Hillmer AT, Rusowicz A, Nabulsi N, Matuskey D, Angarita GA, Najafzadeh S, Kapinos M, Southwick SM, Krystal JH, Carson RE, Huang Y, Cosgrove KP. Imaging brain cortisol regulation in PTSD with a target for 11β-hydroxysteroid dehydrogenase type 1. Journal Of Clinical Investigation 2021, 131: e150452. PMID: 34651587, PMCID: PMC8516462, DOI: 10.1172/jci150452.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderPositron emission tomographyVolume of distributionDehydrogenase type 1Trauma-exposed controlsPTSD groupTranslocator proteinType 1Veterans Affairs (VA) National CenterOverall PTSD severityBrain glucocorticoidBrain immuneMethodsSixteen individualsPeripheral cortisolMicroglial markersImmune suppressionTranslational Science AwardsCortisol levelsNIH National CenterTC groupCortisol regulationEmission tomographyStress disorderLower PTSD symptomsPTSD symptomsRecently Abstinent Smokers Exhibit Mood-Associated Dopamine Dysfunction in the Ventral Striatum Compared to Nonsmokers: A [11C]-(+)-PHNO PET Study
Calakos KC, Hillmer AT, Angarita GA, Baldassarri SR, Najafzadeh S, Emery PR, Matuskey D, Huang Y, Cosgrove KP. Recently Abstinent Smokers Exhibit Mood-Associated Dopamine Dysfunction in the Ventral Striatum Compared to Nonsmokers: A [11C]-(+)-PHNO PET Study. Nicotine & Tobacco Research 2021, 24: 745-752. PMID: 34628508, PMCID: PMC8962719, DOI: 10.1093/ntr/ntab208.Peer-Reviewed Original ResearchConceptsSmoking cessationAbstinent smokersDopamine releaseVentral striatumPercent changeTobacco smokersDopamine dysfunctionDopamine functionPHNO scansPositron emission tomography brainHigher CES-D scoresAbstinent tobacco smokersEarly quit attemptsHuman tobacco smokersPHNO PET StudyStriatal dopamine dysfunctionEpidemiologic Studies Depression ScaleStriatal dopamine releaseChronic nicotine exposureCES-D scoresSmoking cessation attemptNegative mood symptomsReceptor agonist radioligandStriatal dopamine functionLong-term abstinencePET 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
Inverse changes in raphe and cortical 5‐HT1B receptor availability after acute tryptophan depletion in healthy human subjects
Baldassarri SR, Park E, Finnema SJ, Planeta B, Nabulsi N, Najafzadeh S, Ropchan J, Huang Y, Hannestad J, Maloney K, Bhagwagar Z, Carson RE. Inverse changes in raphe and cortical 5‐HT1B receptor availability after acute tryptophan depletion in healthy human subjects. Synapse 2020, 74: e22159. PMID: 32324935, PMCID: PMC7426238, DOI: 10.1002/syn.22159.Peer-Reviewed Original Research
2019
PET Imaging of Pancreatic Dopamine D2 and D3 Receptor Density with 11C-(+)-PHNO in Type 1 Diabetes
Bini J, Sanchez-Rangel E, Gallezot JD, Naganawa M, Nabulsi N, Lim K, Najafzadeh S, Shirali A, Ropchan J, Matuskey D, Huang Y, Herold K, Harris PE, Sherwin RS, Carson RE, Cline GW. PET Imaging of Pancreatic Dopamine D2 and D3 Receptor Density with 11C-(+)-PHNO in Type 1 Diabetes. Journal Of Nuclear Medicine 2019, 61: 570-576. PMID: 31601695, PMCID: PMC7198375, DOI: 10.2967/jnumed.119.234013.Peer-Reviewed Original ResearchConceptsT1DM individualsHealthy controlsDopamine DOutcome measuresAcute C-peptide responseSUVR-1Type 1 diabetes mellitusPET/CT scanningDuration of diabetesMaximal glycemic potentiationC-peptide responseClinical outcome measuresInsulin secretory capacityRoutine clinical measuresD3 receptor densityΒ-cell functionC-peptide releaseQuantitative PET measuresΒ-cell massDynamic PET scansQuantitative outcome measuresAgonist PET radioligandDiabetes mellitusReceptor agonistInsulin antibodiesThe Kappa Opioid Receptor Is Associated With Naltrexone-Induced Reduction of Drinking and Craving
de Laat B, Goldberg A, Shi J, Tetrault JM, Nabulsi N, Zheng MQ, Najafzadeh S, Gao H, Kapinos M, Ropchan J, O'Malley SS, Huang Y, Morris ED, Krishnan-Sarin S. The Kappa Opioid Receptor Is Associated With Naltrexone-Induced Reduction of Drinking and Craving. Biological Psychiatry 2019, 86: 864-871. PMID: 31399255, DOI: 10.1016/j.biopsych.2019.05.021.Peer-Reviewed Original ResearchConceptsKappa-opioid receptorsAlcohol use disorderOpioid receptorsUse disordersNonselective opioid receptor antagonistModest clinical effectsEfficacy of naltrexoneOpioid receptor antagonistDSM-IV criteriaPositron emission tomographyAlcohol Urge QuestionnaireNaltrexone initiationNaltrexone therapyClinical effectsReceptor antagonistTherapeutic effectCingulate cortexDrinking paradigmHeavy drinkersBilateral insulaNaltrexoneAlcohol dependenceBrain regionsEmission tomographyPrefrontal cortexFirst 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 ResearchEvaluation 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
Assessing Synaptic Density in Alzheimer Disease With Synaptic Vesicle Glycoprotein 2A Positron Emission Tomographic Imaging
Chen MK, Mecca AP, Naganawa M, Finnema SJ, Toyonaga T, Lin SF, Najafzadeh S, Ropchan J, Lu Y, McDonald JW, Michalak HR, Nabulsi NB, Arnsten AFT, Huang Y, Carson RE, van Dyck CH. Assessing Synaptic Density in Alzheimer Disease With Synaptic Vesicle Glycoprotein 2A Positron Emission Tomographic Imaging. JAMA Neurology 2018, 75: 1215-1224. PMID: 30014145, PMCID: PMC6233853, DOI: 10.1001/jamaneurol.2018.1836.Peer-Reviewed Original ResearchConceptsPositron emission tomographic imagingSynaptic vesicle glycoprotein 2ASynaptic densityAlzheimer's diseaseEmission tomographic imagingHigh-resolution PET scanningPET scanningCognitive impairmentDisease-modifying therapiesDisease-modifying treatmentsNormal participantsCross-sectional studyPittsburgh compound BMajor structural correlateAmnestic mild cognitive impairmentMagnetic resonance imagingMild cognitive impairmentJ PET imagingRestoration of synapsesSpecific bindingNeurologic evaluationSynaptic lossDisease stagePostmortem studiesOutcome measuresEvaluation of PET Brain Radioligands for Imaging Pancreatic β-Cell Mass: Potential Utility of 11C-(+)-PHNO
Bini J, Naganawa M, Nabulsi N, Huang Y, Ropchan J, Lim K, Najafzadeh S, Herold KC, Cline GW, Carson RE. Evaluation of PET Brain Radioligands for Imaging Pancreatic β-Cell Mass: Potential Utility of 11C-(+)-PHNO. Journal Of Nuclear Medicine 2018, 59: 1249-1254. PMID: 29371405, PMCID: PMC6071501, DOI: 10.2967/jnumed.117.197285.Peer-Reviewed Original ResearchConceptsT1DM subjectsΒ-cell massHealthy controlsΒ-cellsAbdominal organsType 1 diabetes mellitusC-peptide levelsHealthy control subjectsPancreatic β-cell massDeficient insulin secretionReceptor agonist radioligandPET/CTIslets of LangerhansDynamic PET/CTCommon cellular receptorPancreatic bindingDiabetes mellitusDiabetic subjectsControl subjectsNeurologic tissueC-peptideInsulin secretionMean SUVAgonist radioligandDiabetes therapy
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
2015
Test–Retest Reproducibility of Binding Parameters in Humans with 11C-LY2795050, an Antagonist PET Radiotracer for the κ Opioid Receptor
Naganawa M, Zheng MQ, Henry S, Nabulsi N, Lin SF, Ropchan J, Labaree D, Najafzadeh S, Kapinos M, Tauscher J, Neumeister A, Carson RE, Huang Y. Test–Retest Reproducibility of Binding Parameters in Humans with 11C-LY2795050, an Antagonist PET Radiotracer for the κ Opioid Receptor. Journal Of Nuclear Medicine 2015, 56: 243-248. PMID: 25593119, PMCID: PMC4322754, DOI: 10.2967/jnumed.114.147975.Peer-Reviewed Original ResearchConceptsTest-retest variabilityOpioid receptorsOutcome measuresAbsolute test-retest variabilityMultilinear analysis 1Healthy human subjectsSuitable reference regionTest-retest reproducibilityIntraclass correlation coefficientAntagonist radiotracersHealthy subjectsLY2795050PET scansBrain regionsDistribution volumePET radioligandTest-retest performancePET studiesArterial input functionPET radiotracersHuman subjectsReference regionReceptorsVT valuesKOR
2013
Reductions in Brain 5-HT1B Receptor Availability in Primarily Cocaine-Dependent Humans
Matuskey D, Bhagwagar Z, Planeta B, Pittman B, Gallezot JD, Chen J, Wanyiri J, Najafzadeh S, Ropchan J, Geha P, Huang Y, Potenza MN, Neumeister A, Carson RE, Malison RT. Reductions in Brain 5-HT1B Receptor Availability in Primarily Cocaine-Dependent Humans. Biological Psychiatry 2013, 76: 816-822. PMID: 24433854, PMCID: PMC4037398, DOI: 10.1016/j.biopsych.2013.11.022.Peer-Reviewed Original ResearchConceptsRegional binding potentialPositron emission tomographyCocaine dependenceEmission tomographyFrontal cortexReceptor availabilityAge-matched healthy control subjectsSignificant gray matter reductionsYears of cocaineIllicit substance abuseHealthy control subjectsDaily tobacco useCocaine-dependent humansGray matter reductionsEffects of cocaineMagnetic resonance imagingSignificant reductionPreclinical evidenceControl subjectsPrimary addictionSerotonin receptorsHealthy subjectsTobacco useMedication developmentAnterior cingulateTracer Kinetic Modeling of [11C]AFM, a New PET Imaging Agent for the Serotonin Transporter
Naganawa M, Nabulsi N, Planeta B, Gallezot JD, Lin SF, Najafzadeh S, Williams W, Ropchan J, Labaree D, Neumeister A, Huang Y, Carson RE. Tracer Kinetic Modeling of [11C]AFM, a New PET Imaging Agent for the Serotonin Transporter. Cerebrovascular And Brain Metabolism Reviews 2013, 33: 1886-1896. PMID: 23921898, PMCID: PMC3851894, DOI: 10.1038/jcbfm.2013.134.Peer-Reviewed Original ResearchConceptsPositron emission tomographySerotonin transporterReference tissue modelArterial input functionOne-tissue modelMultilinear reference tissue modelNew PET imaging agentTwo-tissue modelPET imaging agentHealthy human brainSuitable PET radioligandNew positron emission tomographySERT densityRegional time-activity curvesTime-activity curvesEmission tomography dataRegional bindingEmission tomographyPET radioligandRoutine useInterest analysisNoninvasive methodPositron emission tomography dataImaging agentHuman brainElevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: a positron emission tomography study
Neumeister A, Normandin MD, Pietrzak RH, Piomelli D, Zheng MQ, Gujarro-Anton A, Potenza MN, Bailey CR, Lin SF, Najafzadeh S, Ropchan J, Henry S, Corsi-Travali S, Carson RE, Huang Y. Elevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: a positron emission tomography study. Molecular Psychiatry 2013, 18: 1034-1040. PMID: 23670490, PMCID: PMC3752332, DOI: 10.1038/mp.2013.61.Peer-Reviewed Original ResearchMeSH KeywordsAdultAmidesAnalysis of VarianceArachidonic AcidsBrainEndocannabinoidsEthanolaminesFemaleGlyceridesHumansHydrocortisoneImidazolesLogistic ModelsMalePalmitic AcidsPiperidinesPolyunsaturated AlkamidesPyrazolesRadionuclide ImagingReceptor, Cannabinoid, CB1Stress Disorders, Post-TraumaticYoung AdultConceptsPost-traumatic stress disorderVolume of distributionCB1 receptor availabilityPositron emission tomographyHC groupReceptor availabilityTC groupCannabinoid type 1 receptorStress disorderPositron emission tomography studyEvidence-based pharmacotherapyEtiology of PTSDType 1 receptorEmission tomography studiesAnandamide concentrationsElevated brainPeripheral levelsHealthy controlsCB1 receptorsUntreated individualsPET scansAnimal modelsCortisol levelsLifetime historyEmission tomography