2016
Age-related changes in binding of the D2/3 receptor radioligand [11C](+)PHNO in healthy volunteers
Matuskey D, Worhunksy P, Correa E, Pittman B, Gallezot JD, Nabulsi N, Ropchan J, Sreeram V, Gudepu R, Gaiser E, Cosgrove K, Ding YS, Potenza MN, Huang Y, Malison RT, Carson RE. Age-related changes in binding of the D2/3 receptor radioligand [11C](+)PHNO in healthy volunteers. NeuroImage 2016, 130: 241-247. PMID: 26876475, PMCID: PMC4808424, DOI: 10.1016/j.neuroimage.2016.02.002.Peer-Reviewed Original ResearchConceptsPositron emission tomographyReceptor availabilitySN/VTADopamine systemMidbrain regionsSubstantia nigra/ventral tegmental areaHealthy control subjectsWhole-brain voxel-wise analysisVentral tegmental areaPrevious imaging studiesVoxel-wise analysisAge-associated declineAge-related changesAntagonist radiotracersExtrastriatal areasReference tissue modelAgonist radiotracerAge-related declineControl subjectsTegmental areaHealthy subjectsHealthy volunteersPositive correlationReceptor radioligandSecondary analysis
2015
Receptor Occupancy of the κ-Opioid Antagonist LY2456302 Measured with Positron Emission Tomography and the Novel Radiotracer 11C-LY2795050
Naganawa M, Dickinson GL, Zheng MQ, Henry S, Vandenhende F, Witcher J, Bell R, Nabulsi N, Lin SF, Ropchan J, Neumeister A, Ranganathan M, Tauscher J, Huang Y, Carson RE. Receptor Occupancy of the κ-Opioid Antagonist LY2456302 Measured with Positron Emission Tomography and the Novel Radiotracer 11C-LY2795050. Journal Of Pharmacology And Experimental Therapeutics 2015, 356: 260-266. PMID: 26628406, PMCID: PMC4727157, DOI: 10.1124/jpet.115.229278.Peer-Reviewed Original ResearchConceptsHours postdosePositron emission tomographyReceptor occupancyEmission tomographySerious adverse eventsSingle oral dosesImportant therapeutic roleΚ-opioid receptorsSubstance abuse disordersFurther clinical testingHealthy human subjectsMultilinear analysis-1 (MA1) methodAntagonist radiotracersAdverse eventsOral dosesBrain penetrationTherapeutic rolePlasma concentrationsAbuse disordersEthanol consumptionLY2456302Clinical testingNovel radiotracersAlcohol dependenceDistribution volumeTest–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
2014
Kinetic Modeling of 11C-LY2795050, A Novel Antagonist Radiotracer for PET Imaging of the Kappa Opioid Receptor in Humans
Naganawa M, Zheng MQ, Nabulsi N, Tomasi G, Henry S, Lin SF, Ropchan J, Labaree D, Tauscher J, Neumeister A, Carson RE, Huang Y. Kinetic Modeling of 11C-LY2795050, A Novel Antagonist Radiotracer for PET Imaging of the Kappa Opioid Receptor in Humans. Cerebrovascular And Brain Metabolism Reviews 2014, 34: 1818-1825. PMID: 25182664, PMCID: PMC4269759, DOI: 10.1038/jcbfm.2014.150.Peer-Reviewed Original ResearchConceptsKappa-opioid receptorsMultilinear analysis 1Opioid receptorsNovel kappa opioid receptorDistribution volumePositron emission tomography (PET) imagingEmission Tomography ImagingLow intersubject variabilityTwo-tissue compartment modelAntagonist radiotracersOral naltrexoneNondisplaceable distribution volumeBaseline scanLY2795050Human studiesArterial input functionPET imagingTomography imagingIntersubject variabilityNaltrexone
2013
Synthesis and Evaluation of 11C-LY2795050 as a κ-Opioid Receptor Antagonist Radiotracer for PET Imaging
Zheng MQ, Nabulsi N, Kim SJ, Tomasi G, Lin SF, Mitch C, Quimby S, Barth V, Rash K, Masters J, Navarro A, Seest E, Morris ED, Carson RE, Huang Y. Synthesis and Evaluation of 11C-LY2795050 as a κ-Opioid Receptor Antagonist Radiotracer for PET Imaging. Journal Of Nuclear Medicine 2013, 54: 455-463. PMID: 23353688, PMCID: PMC3775344, DOI: 10.2967/jnumed.112.109512.Peer-Reviewed Original ResearchConceptsKappa-opioid receptorsAntagonist radiotracersSelective kappa opioid receptorPET imagingKOR knockout micePathophysiology of depressionSelective KOR antagonistRadioligand competition binding assaysEx vivo analysisDose-dependent mannerFavorable pharmacokinetic propertiesFull antagonist activityKOR antagonistsPeripheral metabolismKOR agonistsTracer candidatesLY2795050Sprague-DawleyAntagonist tracersKnockout miceSpecific binding signalsCompetition binding assaysRhesus monkeysPharmacokinetic propertiesAntagonist activity