2019
Kappa-opioid receptors, dynorphin, and cocaine addiction: a positron emission tomography study
Martinez D, Slifstein M, Matuskey D, Nabulsi N, Zheng MQ, Lin SF, Ropchan J, Urban N, Grassetti A, Chang D, Salling M, Foltin R, Carson RE, Huang Y. Kappa-opioid receptors, dynorphin, and cocaine addiction: a positron emission tomography study. Neuropsychopharmacology 2019, 44: 1720-1727. PMID: 31026862, PMCID: PMC6785004, DOI: 10.1038/s41386-019-0398-4.Peer-Reviewed Original ResearchConceptsCocaine use disorderStress-induced relapsePositron emission tomographyCocaine bingeKappa-opioid receptor/dynorphin systemKOR selective agonistPositron emission tomography studyKappa-opioid receptorsCold pressor testCocaine self-administration sessionsEmission tomography studiesSelf-administration sessionsStress-induced cocaineEndogenous dynorphinDynorphin systemHealthy controlsPressor testSelective agonistPET scansAnimal studiesKOR bindingReceptor availabilitySignificant associationBrain regionsEmission tomography
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
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
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