2023
Imaging the brain’s immune response to alcohol with [11C]PBR28 TSPO Positron Emission Tomography
Raval N, Angarita G, Matuskey D, Miller R, Drake L, Kapinos M, Nabulsi N, Huang Y, Carson R, O’Malley S, Cosgrove K, Hillmer A. Imaging the brain’s immune response to alcohol with [11C]PBR28 TSPO Positron Emission Tomography. Molecular Psychiatry 2023, 28: 3384-3390. PMID: 37532797, PMCID: PMC10743097, DOI: 10.1038/s41380-023-02198-6.Peer-Reviewed Original ResearchConceptsVolume of distributionBlood alcohol levelsPositron emission tomographyBrain immune responseImmune responseAlcohol challengeEmission tomographyPeak blood alcohol levelsMultilinear analysis 1Peripheral immune functionVivo human evidenceLaboratory alcohol challengeTSPO positron emission tomographyBinge levelsPlasma cytokinesImmune dysfunctionNeuroimmune systemIL-6MCP-1Cytokines TNFAcute effectsScan dayArterial bloodHuman evidenceImmune functionPreclinical 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
Lower prefrontal cortical synaptic vesicle binding in cocaine use disorder: An exploratory 11C‐UCB‐J positron emission tomography study in humans
Angarita GA, Worhunsky PD, Naganawa M, Toyonaga T, Nabulsi NB, Li C, Esterlis I, Skosnik PD, Radhakrishnan R, Pittman B, Gueorguieva R, Potenza MN, Finnema SJ, Huang Y, Carson RE, Malison RT. Lower prefrontal cortical synaptic vesicle binding in cocaine use disorder: An exploratory 11C‐UCB‐J positron emission tomography study in humans. Addiction Biology 2021, 27: e13123. PMID: 34852401, PMCID: PMC8891080, DOI: 10.1111/adb.13123.Peer-Reviewed Original ResearchConceptsCocaine use disorderAnterior cingulate cortexRecent cocaine useSynaptic densityMedial orbitofrontal cortexPrefrontal cortexCocaine useOrbitofrontal cortexUse disordersVentromedial prefrontal cortexPositron emission tomography scanPositron emission tomography studyEmission tomography scanSynaptic vesicle glycoprotein 2AHealthy control subjectsVolume of distributionEmission tomography studiesAcute cocaineControl subjectsTomography scanCocaine exposurePreclinical studiesHC subjectsDendritic spinesLifetime cocaine useA 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 characterizationImaging 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 symptoms
2020
Binding of the synaptic vesicle radiotracer [11C]UCB-J is unchanged during functional brain activation using a visual stimulation task
Smart K, Liu H, Matuskey D, Chen MK, Torres K, Nabulsi N, Labaree D, Ropchan J, Hillmer AT, Huang Y, Carson RE. Binding of the synaptic vesicle radiotracer [11C]UCB-J is unchanged during functional brain activation using a visual stimulation task. Cerebrovascular And Brain Metabolism Reviews 2020, 41: 1067-1079. PMID: 32757741, PMCID: PMC8054713, DOI: 10.1177/0271678x20946198.Peer-Reviewed Original ResearchConceptsVisual cortexVisual stimulationPositron emission tomography radioligandBrain activationBlood flow increasesVolume of distributionPrimary visual cortexCheckerboard visual stimulationFunctional brain activationFunctional magnetic resonanceReference tissue modelFMRI BOLD responsesSynaptic densityVisual stimulation taskOne-tissue compartment modelHealthy volunteersNeuronal firingTomography radioligandPET scansTissue influxVivo measuresRobust increaseBOLD responseTracer influxStimulation task
2019
In vivo evidence for dysregulation of mGluR5 as a biomarker of suicidal ideation
Davis MT, Hillmer A, Holmes SE, Pietrzak RH, DellaGioia N, Nabulsi N, Matuskey D, Angarita G, Carson RE, Krystal JH, Esterlis I. In vivo evidence for dysregulation of mGluR5 as a biomarker of suicidal ideation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 11490-11495. PMID: 31085640, PMCID: PMC6561298, DOI: 10.1073/pnas.1818871116.Peer-Reviewed Original ResearchConceptsMGluR5 availabilitySuicidal ideationHC individualsPathophysiology of PTSDLimbic brain regionsVolume of distributionHealthy comparison controlsSuicide risk managementPositron emission tomographyReceptor 5Venous input functionsBrain regionsPTSD individualsEmission tomographyMDD individualsVivo evidenceRecent evidencePotential roleMGluR5PTSDComparison controlsDysregulationMDDIdeationIndividuals
2018
PET imaging reveals lower kappa opioid receptor availability in alcoholics but no effect of age
Vijay A, Cavallo D, Goldberg A, de Laat B, Nabulsi N, Huang Y, Krishnan-Sarin S, Morris ED. PET imaging reveals lower kappa opioid receptor availability in alcoholics but no effect of age. Neuropsychopharmacology 2018, 43: 2539-2547. PMID: 30188515, PMCID: PMC6224533, DOI: 10.1038/s41386-018-0199-1.Peer-Reviewed Original ResearchConceptsHealthy control cohortVolume of distributionOpioid receptor systemKappa-opioid receptorsOpioid receptorsDelta opioid receptor systemReceptor systemMu-opioid receptor systemOpioid receptor availabilityPotential pharmacological targetEffect of ageAge-related declineControl cohortPET scansAntagonist tracersReceptor availabilityMultivariate analysisPharmacological targetsPET imagingReceptorsAgePartial volume correctionCohortVT valuesPresent study
2016
PET imaging reveals sex differences in kappa opioid receptor availability in humans, in vivo.
Vijay A, Wang S, Worhunsky P, Zheng MQ, Nabulsi N, Ropchan J, Krishnan-Sarin S, Huang Y, Morris ED. PET imaging reveals sex differences in kappa opioid receptor availability in humans, in vivo. Am J Nucl Med Mol Imaging 2016, 6: 205-14. PMID: 27648372, PMCID: PMC5004062.Peer-Reviewed Original ResearchKappa-opioid receptorsOpioid receptorsSex differencesOpioid receptor availabilityTreatment of painHealthy control menDelta-opioid receptorsVolume of distributionEfficacy of treatmentKappa opioid analgesicsMultiple brain regionsOpioid analgesicsKOR systemControl menAntagonist tracersPET scansReceptor availabilityVoxel levelPharmacological targetsBrain regionsPET imagingAddiction withdrawalReceptorsTreatmentPartial volume correction
2014
In Vivo Ketamine-Induced Changes in [11C]ABP688 Binding to Metabotropic Glutamate Receptor Subtype 5
DeLorenzo C, DellaGioia N, Bloch M, Sanacora G, Nabulsi N, Abdallah C, Yang J, Wen R, Mann JJ, Krystal JH, Parsey RV, Carson RE, Esterlis I. In Vivo Ketamine-Induced Changes in [11C]ABP688 Binding to Metabotropic Glutamate Receptor Subtype 5. Biological Psychiatry 2014, 77: 266-275. PMID: 25156701, PMCID: PMC4277907, DOI: 10.1016/j.biopsych.2014.06.024.Peer-Reviewed Original ResearchConceptsSubtype 5Ketamine administrationPET scansMetabotropic glutamate receptor subtype 5Prefrontal cortexAspartate glutamate receptor antagonistIntravenous ketamine administrationKetamine-induced effectsPositron emission tomography (PET) ligandGlutamate receptor antagonistsVolume of distributionMedial prefrontal cortexNegative allosteric modulatorsKetamine initiationGlutamate releaseDorsal putamenKetamine responseSubanesthetic dosesOrbital prefrontal cortexReceptor antagonistAcute effectsBolus injectionDorsal caudateArterial bloodScan 1
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