2024
Microglia-mediated neuroimmune suppression in PTSD is associated with anhedonia
Bonomi R, Hillmer A, Woodcock E, Bhatt S, Rusowicz A, Angarita G, Carson R, Davis M, Esterlis I, Nabulsi N, Huang Y, Krystal J, Pietrzak R, Cosgrove K. Microglia-mediated neuroimmune suppression in PTSD is associated with anhedonia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2406005121. PMID: 39172786, PMCID: PMC11363315, DOI: 10.1073/pnas.2406005121.Peer-Reviewed Original ResearchConceptsPTSD groupPrefrontal-limbic circuitsNeuroimmune responseAssociated with anhedoniaPosttraumatic stress disorderPositron emission tomography brain imagingTranslocator protein availabilityBrain immune functionAnhedonic symptomsStress disorderPeripheral immune dysfunctionPTSDGroup differencesSeverity of symptomsPsychiatric diseasesTranslocator proteinBrain imagingAdministration of lipopolysaccharideSymptomsMicroglial markersLPS-induced increaseCompared to controlsImmune functionSickness symptomsAnhedonia
2023
Evaluation of a First PET Tracer Suitable for Imaging the Sigma‑2 Receptor in the Brain of Nonhuman Primates
Alluri S, Zheng M, Holden D, Zhang Y, Zhang L, Felchner Z, Li S, Ropchan J, Carson R, Jia H, Huang Y. Evaluation of a First PET Tracer Suitable for Imaging the Sigma‑2 Receptor in the Brain of Nonhuman Primates. Molecular Pharmaceutics 2023, 21: 194-200. PMID: 38013422, DOI: 10.1021/acs.molpharmaceut.3c00750.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseLimited brain uptakeNonhuman primate brainCentral nervous systemPotential therapeutic targetPositron emission tomography (PET) imagingEmission Tomography ImagingTransmembrane protein 97Sigma-2 receptorsFirst PET tracerBrain penetrantBrain uptakeTherapeutic targetNervous systemPrimate brainNeurological disordersPET tracersNonhuman primatesTomography imagingProtein 97CancerDiseaseBrainCell typesReceptorsImaging 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 functionPrincipal component analysis of synaptic density measured with [11C]UCB-J PET in early Alzheimer’s disease
O'Dell R, Higgins-Chen A, Gupta D, Chen M, Naganawa M, Toyonaga T, Lu Y, Ni G, Chupak A, Zhao W, Salardini E, Nabulsi N, Huang Y, Arnsten A, Carson R, van Dyck C, Mecca A. Principal component analysis of synaptic density measured with [11C]UCB-J PET in early Alzheimer’s disease. NeuroImage Clinical 2023, 39: 103457. PMID: 37422964, PMCID: PMC10338149, DOI: 10.1016/j.nicl.2023.103457.Peer-Reviewed Original ResearchConceptsCognitive domainsCognitive performanceSubjects' scoresCortical regionsNeuropsychological batteryEarly Alzheimer's diseaseAD groupBilateral regionsNormal participantsNegative loadingsCognitive impairmentCN participantsAlzheimer's diseaseParticipantsStructural correlatesStrong contributionParticipant characteristicsScoresPositive loadingsData-driven approachTotal variancePrincipal component analysisSpecific spatial patternsPreclinical 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 trialsInvestigating CNS distribution of PF‐05212377, a P‐glycoprotein substrate, by translation of 5‐HT6 receptor occupancy from non‐human primates to humans
Sawant‐Basak A, Chen L, Lockwood P, Boyden T, Doran A, Mancuso J, Zasadny K, McCarthy T, Morris E, Carson R, Esterlis I, Huang Y, Nabulsi N, Planeta B, Fullerton T. Investigating CNS distribution of PF‐05212377, a P‐glycoprotein substrate, by translation of 5‐HT6 receptor occupancy from non‐human primates to humans. Biopharmaceutics & Drug Disposition 2023, 44: 48-59. PMID: 36825693, DOI: 10.1002/bdd.2351.Peer-Reviewed Original ResearchConceptsNon-human primatesBrain penetrationPositron emission tomographyReceptor occupancyUnbound concentrationsPre-clinical evidenceVivo brain penetrationConcentration-dependent increaseP-glycoprotein substratesPlasma ECsP-gpAlzheimer's diseaseEmission tomographyRat BBBTarget engagementCumulative evidenceDependent increaseTransporter substratesCNS distributionBBBRatsDiseasePrimatesSpecies differencesHumansCholinergic system adaptations are associated with cognitive function in people recently abstinent from smoking: a (-)-[18F]flubatine PET study
Calakos K, Hillmer A, Anderson J, LeVasseur B, Baldassarri S, Angarita G, Matuskey D, Kapinos M, Zheng M, Huang Y, Cosgrove K. Cholinergic system adaptations are associated with cognitive function in people recently abstinent from smoking: a (-)-[18F]flubatine PET study. Neuropsychopharmacology 2023, 48: 683-689. PMID: 36681758, PMCID: PMC9938267, DOI: 10.1038/s41386-023-01535-1.Peer-Reviewed Original ResearchConceptsExecutive functionCholinergic systemWorse executive functionAcetylcholine levelsVerbal learningCognitive batteryPositron emission tomography brainCognitive dataAbstinent smokersCognitive functionCognitive deficitsCortical acetylcholine levelsEarly smoking cessationAcetylcholinesterase inhibitor physostigmineCognitionQuit attemptsNAChR sitesPhysostigmine administrationTomography brainSmoking statusSmoking cessationInhibitor physostigmineTreatment strategiesAgonist radioligandPhysostigmine challenge
2022
Neurotransmitter transporter occupancy following administration of centanafadine sustained-release tablets: A phase 1 study in healthy male adults
Matuskey D, Gallezot J, Nabulsi N, Henry S, Torres K, Dias M, Angarita G, Huang Y, Shoaf S, Carson R, Mehrotra S. Neurotransmitter transporter occupancy following administration of centanafadine sustained-release tablets: A phase 1 study in healthy male adults. Journal Of Psychopharmacology 2022, 37: 164-171. PMID: 36515395, PMCID: PMC9912308, DOI: 10.1177/02698811221140008.Peer-Reviewed Original Research
2019
The 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 cortex
2018
Evaluation 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
2001
Vulnerability of positron emission tomography radiotracers to endogenous competition. New insights.
Laruelle M, Huang Y. Vulnerability of positron emission tomography radiotracers to endogenous competition. New insights. Quarterly Journal Of Nuclear Medicine And Molecular Imaging 2001, 45: 124-38. PMID: 11476162.Peer-Reviewed Original ResearchConceptsTransmitter levelsSynaptic dopamine concentrationsPositron emission tomographyDA transmissionD2 receptorsNeurotransmitter systemsPharmacological challengeDevelopment of PETSynaptic transmitter levelsEmission tomographyDopamine concentrationsAcute fluctuationsReceptor traffickingHuman brainRadioligandImaging techniquesVivoEndogenous competitionPETBinding competitionNeurotransmittersBrainReceptorsAnalyses of [18F]altanserin bolus injection PET data. I: Consideration of radiolabeled metabolites in baboons
Price J, Lopresti B, Mason N, Holt D, Huang Y, Mathis C. Analyses of [18F]altanserin bolus injection PET data. I: Consideration of radiolabeled metabolites in baboons. Synapse 2001, 41: 1-10. PMID: 11354008, DOI: 10.1002/syn.1054.Peer-Reviewed Original ResearchConceptsBolus injectionMajor radiometabolitePositron emission tomographySerotonin 2A receptor bindingBlood-brain barrier passageReceptor-rich regionsKetanserin administrationNonspecific radioactivityReceptor blockadeInput function methodEmission tomographyPET studiesPET dataReceptor bindingRadiometabolitesVivo kineticsInjectionBBBTissue componentsHuman brainBaboonsMetabolitesRadioactivityBlockadeAntagonistDifferential Occupancy of Somatodendritic and Postsynaptic 5HT1A Receptors by Pindolol: A Dose-Occupancy Study with [11C]WAY 100635 and Positron Emission Tomography in Humans
Martinez D, Hwang D, Mawlawi O, Slifstein M, Kent J, Simpson N, Parsey R, Hashimoto T, Huang Y, Shinn A, Van Heertum R, Abi-Dargham A, Caltabiano S, Malizia A, Cowley H, Mann J, Laruelle M. Differential Occupancy of Somatodendritic and Postsynaptic 5HT1A Receptors by Pindolol: A Dose-Occupancy Study with [11C]WAY 100635 and Positron Emission Tomography in Humans. Neuropsychopharmacology 2001, 24: 209-229. PMID: 11166513, DOI: 10.1016/s0893-133x(00)00187-1.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntidepressive AgentsBrainHumansKineticsMagnetic Resonance ImagingMaleMood DisordersPindololPiperazinesPyridinesRaphe NucleiReceptors, NeurotransmitterReceptors, SerotoninReceptors, Serotonin, 5-HT1Selective Serotonin Reuptake InhibitorsSynaptic TransmissionTomography, Emission-ComputedConceptsDorsal raphe nucleusPositron emission tomographyClinical studiesSelective serotonin reuptake inhibitor (SSRI) therapyPlacebo-controlled clinical studySerotonin reuptake inhibitor therapyEmission tomographyAbility of pindololPindolol augmentationAntidepressant therapyAntidepressant treatmentClinical responseInhibitor therapyRaphe nucleusScan 3Scan 4Therapeutic effectHealthy volunteersScan 2Vivo selectivityPindololAutoreceptorsSSRIsTherapyInconsistent results
1999
Pet imaging of serotonin 1A receptor binding in depression
Drevets W, Frank E, Price J, Kupfer D, Holt D, Greer P, Huang Y, Gautier C, Mathis C. Pet imaging of serotonin 1A receptor binding in depression. Biological Psychiatry 1999, 46: 1375-1387. PMID: 10578452, DOI: 10.1016/s0006-3223(99)00189-4.Peer-Reviewed Original ResearchConceptsFamilial mood disordersReceptor BPPostmortem studiesMood disordersMesiotemporal cortexMidbrain rapheSerotonin 1A receptor systemBrain regionsPET imagingPrevious postmortem studiesSerotonin 1A receptorMultiple brain regionsHistopathological changesHealthy controlsBP valuesMajor depressionDepressed phasePostcentral gyrusClinical conditionsOccipital cortexBipolar relativesBipolar depressivesReceptor radioligandDepressed subjectsNormal baseline
1998
Test–retest variability of serotonin 5‐HT2A receptor binding measured with positron emission tomography and [18F]altanserin in the human brain
Smith G, Price J, Lopresti B, Huang Y, Simpson N, Holt D, Mason N, Meltzer C, Sweet R, Nichols T, Sashin D, Mathis C. Test–retest variability of serotonin 5‐HT2A receptor binding measured with positron emission tomography and [18F]altanserin in the human brain. Synapse 1998, 30: 380-392. PMID: 9826230, DOI: 10.1002/(sici)1098-2396(199812)30:4<380::aid-syn5>3.0.co;2-u.Peer-Reviewed Original Research