2020
Kinetic Modeling and Test–Retest Reproducibility of 11C-EKAP and 11C-FEKAP, Novel Agonist Radiotracers for PET Imaging of the κ-Opioid Receptor in Humans
Naganawa M, Li S, Nabulsi N, Lin SF, Labaree D, Ropchan J, Gao H, Mei M, Henry S, Matuskey D, Carson RE, Huang Y. Kinetic Modeling and Test–Retest Reproducibility of 11C-EKAP and 11C-FEKAP, Novel Agonist Radiotracers for PET Imaging of the κ-Opioid Receptor in Humans. Journal Of Nuclear Medicine 2020, 61: 1636-1642. PMID: 32169917, PMCID: PMC9364890, DOI: 10.2967/jnumed.119.227694.Peer-Reviewed Original Research
2019
Social status and demographic effects of the kappa opioid receptor: a PET imaging study with a novel agonist radiotracer in healthy volunteers
Matuskey D, Dias M, Naganawa M, Pittman B, Henry S, Li S, Gao H, Ropchan J, Nabulsi N, Carson RE, Huang Y. Social status and demographic effects of the kappa opioid receptor: a PET imaging study with a novel agonist radiotracer in healthy volunteers. Neuropsychopharmacology 2019, 44: 1714-1719. PMID: 30928993, PMCID: PMC6785144, DOI: 10.1038/s41386-019-0379-7.Peer-Reviewed Original ResearchConceptsBody mass indexKappa-opioid receptorsPositron emission tomographyAgonist radiotracerKOR systemOpioid receptorsTime-activity curvesBarratt Simplified MeasureAnterior cingulate cortexArterial blood samplingMultilinear analysis-1 (MA1) methodPET imaging studiesKOR levelsMass indexPreclinical modelsFrontal cortexHealthy volunteersRegional time-activity curvesBlood samplingPET scansCingulate cortexImaging studiesEmission tomographyVentral striatumRegional volumesNovel Kappa Opioid Receptor Agonist as Improved PET Radiotracer: Development and in Vivo Evaluation
Li S, Zheng M, Naganawa M, Gao H, Pracitto R, Shirali A, Lin SF, Teng JK, Ropchan J, Huang Y. Novel Kappa Opioid Receptor Agonist as Improved PET Radiotracer: Development and in Vivo Evaluation. Molecular Pharmaceutics 2019, 16: 1523-1531. PMID: 30726092, DOI: 10.1021/acs.molpharmaceut.8b01209.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainCarbon RadioisotopesMacaca mulattaPiperazinesPositron-Emission TomographyRadioactive TracersRadiopharmaceuticalsReceptors, Opioid, kappaTissue DistributionConceptsKappa-opioid receptorsAgonist radiotracerOpioid receptorsNovel kappa-opioid receptor agonistKappa-opioid receptor agonistFast tissue kineticsNonselective opioid receptorTissue kineticsOpioid receptor agonistsDose-dependent mannerMultilinear analysis-1 (MA1) methodHigh specific bindingSpecific bindingAgonist tracersHigh binding regionsReceptor agonistRegional time-activity curvesSpecific binding signalsTime-activity curvesArterial activityImproved imaging propertiesRhesus monkeysDrug abusePET radiotracersParent fractionDevelopment and In Vivo Evaluation of a κ-Opioid Receptor Agonist as a PET Radiotracer with Superior Imaging Characteristics
Li S, Zheng MQ, Naganawa M, Kim S, Gao H, Kapinos M, Labaree D, Huang Y. Development and In Vivo Evaluation of a κ-Opioid Receptor Agonist as a PET Radiotracer with Superior Imaging Characteristics. Journal Of Nuclear Medicine 2019, 60: 1023-1030. PMID: 30630942, PMCID: PMC6604690, DOI: 10.2967/jnumed.118.220517.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsMacaca mulattaPiperazinePiperazinesPositron-Emission TomographyRadioactive TracersRadiochemistryReceptors, Opioid, kappaConceptsMultilinear analysis 1Κ-opioid receptor agonistCentral nervous system diseaseNervous system diseasesHigh specific bindingAgonist tracersGlobus pallidusReceptor abnormalitiesReceptor agonistFrontal cortexSystem diseasesPrimate brainReceptor occupancySuperior imaging characteristicsCingulate cortexAlzheimer's diseasePeak uptakeImaging characteristicsRhesus monkeysOptimal radiotracerPET studiesArterial input functionBlocking studiesPET radiotracersAnalysis 1
2017
Quantitative PET Imaging in Drug Development: Estimation of Target Occupancy
Naganawa M, Gallezot JD, Rossano S, Carson RE. Quantitative PET Imaging in Drug Development: Estimation of Target Occupancy. Bulletin Of Mathematical Biology 2017, 81: 3508-3541. PMID: 29230702, DOI: 10.1007/s11538-017-0374-2.Peer-Reviewed Original ResearchNovel 18F-Labeled κ-Opioid Receptor Antagonist as PET Radiotracer: Synthesis and In Vivo Evaluation of 18F-LY2459989 in Nonhuman Primates
Li S, Cai Z, Zheng MQ, Holden D, Naganawa M, Lin SF, Ropchan J, Labaree D, Kapinos M, Lara-Jaime T, Navarro A, Huang Y. Novel 18F-Labeled κ-Opioid Receptor Antagonist as PET Radiotracer: Synthesis and In Vivo Evaluation of 18F-LY2459989 in Nonhuman Primates. Journal Of Nuclear Medicine 2017, 59: 140-146. PMID: 28747521, PMCID: PMC5750518, DOI: 10.2967/jnumed.117.195586.Peer-Reviewed Original ResearchConceptsPET radiotracersNonhuman primatesTime-activity curvesHigh specific binding signalsΚ-opioid receptor antagonistCentral nervous system disordersFast tissue kineticsBrain time-activity curvesCaudate/putamenNervous system disordersΚ-opioid receptorsRegional binding potentialPeak uptake timeRegional distribution volumesAntagonist radiotracersReceptor antagonistFrontal cortexNovel 18FRegional time-activity curvesSystem disordersNovel radioligandPET scansSpecific binding signalsTemporal cortexMonkey brain
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 ResearchMeSH KeywordsAdultBenzamidesBrainCarbon RadioisotopesHumansMaleMiddle AgedPositron-Emission TomographyPyrrolidinesReceptors, Opioid, kappaYoung AdultConceptsHours 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 variabilityNaltrexoneEvaluation of the agonist PET radioligand [11C]GR103545 to image kappa opioid receptor in humans: Kinetic model selection, test–retest reproducibility and receptor occupancy by the antagonist PF-04455242
Naganawa M, Jacobsen LK, Zheng MQ, Lin SF, Banerjee A, Byon W, Weinzimmer D, Tomasi G, Nabulsi N, Grimwood S, Badura LL, Carson RE, McCarthy TJ, Huang Y. Evaluation of the agonist PET radioligand [11C]GR103545 to image kappa opioid receptor in humans: Kinetic model selection, test–retest reproducibility and receptor occupancy by the antagonist PF-04455242. NeuroImage 2014, 99: 69-79. PMID: 24844744, PMCID: PMC4140089, DOI: 10.1016/j.neuroimage.2014.05.033.Peer-Reviewed Original ResearchConceptsKappa-opioid receptorsTest-retest reproducibilityTest-retest variabilityAbsolute test-retest variabilityPF-04455242Time-activity curvesIntra-class coefficientOpioid receptorsRegional time-activity curvesMetabolite-corrected arterial input functionHuman positron emission tomography studiesPositron emission tomography studySelective KOR antagonistEmission tomography studiesReceptor occupancy studiesSuitable reference regionHalf maximal inhibitory concentrationAgonist tracersRegional VTAgonist PET radioligandOral doseKOR antagonistsMaximal inhibitory concentrationOral administrationPreclinical models