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 ResearchMeSH KeywordsAnimalsBrainMacaca mulattaNeoplasmsPositron-Emission TomographyPrimatesRadiopharmaceuticalsConceptsAlzheimer'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 typesReceptors
2022
Comparison of three novel radiotracers for GluN2B-containing NMDA receptors in non-human primates: (R)-[11C]NR2B-Me, (R)-[18F]of-Me-NB1, and (S)-[18F]of-NB1
Smart K, Zheng MQ, Ahmed H, Fang H, Xu Y, Cai L, Holden D, Kapinos M, Haider A, Felchner Z, Ropchan JR, Tamagnan G, Innis RB, Pike VW, Ametamey SM, Huang Y, Carson RE. Comparison of three novel radiotracers for GluN2B-containing NMDA receptors in non-human primates: (R)-[11C]NR2B-Me, (R)-[18F]of-Me-NB1, and (S)-[18F]of-NB1. Cerebrovascular And Brain Metabolism Reviews 2022, 42: 1398-1409. PMID: 35209743, PMCID: PMC9274863, DOI: 10.1177/0271678x221084416.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainMacaca mulattaPositron-Emission TomographyRadiopharmaceuticalsReceptors, N-Methyl-D-AspartateConceptsNon-human primatesNMDA receptorsML/GluN2B-containing NMDA receptorsFree fractionRegional non-displaceable binding potentialsNon-displaceable binding potentialGood brain uptakeAdult rhesus macaquesBrain uptakeOne-tissue compartment modelTime-activity curvesNovel radiotracersGray matterNeuropsychiatric disordersSelective radiotracerDisplaceable bindingRhesus macaquesTissue distributionAcceptable profilePotential translationRadiotracerCerebellumFurther investigationReceptorsCharacterization in nonhuman primates of (R)-[18F]OF-Me-NB1 and (S)-[18F]OF-Me-NB1 for imaging the GluN2B subunits of the NMDA receptor
Zheng M, Ahmed H, Smart K, Xu Y, Holden D, Kapinos M, Felchner Z, Haider A, Tamagnan G, Carson RE, Huang Y, Ametamey SM. Characterization in nonhuman primates of (R)-[18F]OF-Me-NB1 and (S)-[18F]OF-Me-NB1 for imaging the GluN2B subunits of the NMDA receptor. European Journal Of Nuclear Medicine And Molecular Imaging 2022, 49: 2153-2162. PMID: 35107627, PMCID: PMC9165293, DOI: 10.1007/s00259-022-05698-9.Peer-Reviewed Original Research
2021
A 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 ResearchMeSH KeywordsAminoacridinesAnimalsBrainHumansMembrane GlycoproteinsPositron-Emission TomographyRadiopharmaceuticalsSynaptic VesiclesConceptsTest-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 characterizationAssessment of test-retest reproducibility of [18F]SynVesT-1, a novel radiotracer for PET imaging of synaptic vesicle glycoprotein 2A
Li S, Naganawa M, Pracitto R, Najafzadeh S, Holden D, Henry S, Matuskey D, Emery PR, Cai Z, Ropchan J, Nabulsi N, Carson RE, Huang Y. Assessment of test-retest reproducibility of [18F]SynVesT-1, a novel radiotracer for PET imaging of synaptic vesicle glycoprotein 2A. European Journal Of Nuclear Medicine And Molecular Imaging 2021, 48: 1327-1338. PMID: 33416954, DOI: 10.1007/s00259-020-05149-3.Peer-Reviewed Original ResearchConceptsTest-retest reproducibilityTime-activity curvesBPND valuesNonhuman primatesAbsolute test-retest variabilitySynaptic vesicle glycoprotein 2AHigh brain uptakeNon-displaceable binding potentialExcellent test-retest reproducibilityGray matter areasHealthy human subjectsHigh uptakeTest-retest variabilityDynamic PET scanningTest-retest reliabilityBrain uptakeDistribution volume valuesCentrum semiovaleUrinary bladderOne-tissue compartment modelMaximum SUVPET scanningPET scansTracer uptakeBrain disorders
2020
Positron Emission Tomography Imaging Evaluation of a Novel 18F‑Labeled Sigma‑1 Receptor Radioligand in Cynomolgus Monkeys
Jia H, Cai Z, Holden D, He Y, Lin SF, Li S, Baum E, Shirali A, Kapinos M, Gao H, Ropchan J, Huang Y. Positron Emission Tomography Imaging Evaluation of a Novel 18F‑Labeled Sigma‑1 Receptor Radioligand in Cynomolgus Monkeys. ACS Chemical Neuroscience 2020, 11: 1673-1681. PMID: 32356969, DOI: 10.1021/acschemneuro.0c00171.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainFluorine RadioisotopesMacaca fascicularisPositron-Emission TomographyRadiopharmaceuticalsReceptors, sigma
2019
Imaging histamine H3 receptors with [18F]FMH3: Test–retest and occupancy studies in the non‐human primate
Sandiego CM, Barret O, Lee H, Alagille D, Amenta A, Fowles K, Holden D, Seibyl JP, Tamagnan G. Imaging histamine H3 receptors with [18F]FMH3: Test–retest and occupancy studies in the non‐human primate. Synapse 2019, 73: e22096. PMID: 30835877, DOI: 10.1002/syn.22096.Peer-Reviewed Original ResearchConceptsABT-239Non-human primatesClinical investigationPositron emission tomography radioligandVolume of distributionReceptor subtype 3Histamine H3 receptorsDose-dependent effectAdult female baboonsPET brain scansBrain stemPlasma levelsSleep abnormalitiesBaseline scanH3 receptorsTomography radioligandOccupancy studiesCognitive disordersSubtype 3Brain scansBrain regionsCortical regionsPET studiesCiproxifanBaseline VEvaluation of 11C-LSN3172176 as a Novel PET Tracer for Imaging M1 Muscarinic Acetylcholine Receptors in Nonhuman Primates
Nabulsi NB, Holden D, Zheng MQ, Bois F, Lin SF, Najafzadeh S, Gao H, Ropchan J, Lara-Jaime T, Labaree D, Shirali A, Slieker L, Jesudason C, Barth V, Navarro A, Kant N, Carson RE, Huang Y. Evaluation of 11C-LSN3172176 as a Novel PET Tracer for Imaging M1 Muscarinic Acetylcholine Receptors in Nonhuman Primates. Journal Of Nuclear Medicine 2019, 60: 1147-1153. PMID: 30733324, DOI: 10.2967/jnumed.118.222034.Peer-Reviewed Original ResearchConceptsMuscarinic acetylcholine receptorsAcetylcholine receptorsNonhuman primatesM1 muscarinic acetylcholine receptorBrain time-activity curvesRich brain regionsArterial blood samplingNovel PET tracersSuitable reference regionRegional distribution volumesReference regionDevelopment of drugsBrain uptakeGlobus pallidusDistribution volume valuesNucleus accumbensBlood samplingPET scansTime-activity curvesCognitive impairmentAlzheimer's diseaseBrain regionsDistribution volumeSelective radiotracerRhesus monkeysA Novel 18F‑Labeled Radioligand for Positron Emission Tomography Imaging of 11β-Hydroxysteroid Dehydrogenase (11β-HSD1): Synthesis and Preliminary Evaluation in Nonhuman Primates
Baum E, Zhang W, Li S, Cai Z, Holden D, Huang Y. A Novel 18F‑Labeled Radioligand for Positron Emission Tomography Imaging of 11β-Hydroxysteroid Dehydrogenase (11β-HSD1): Synthesis and Preliminary Evaluation in Nonhuman Primates. ACS Chemical Neuroscience 2019, 10: 2450-2458. PMID: 30689943, DOI: 10.1021/acschemneuro.8b00715.Peer-Reviewed Original Research
2018
Synthesis and in Vivo Evaluation of a Novel PET Radiotracer for Imaging of Synaptic Vesicle Glycoprotein 2A (SV2A) in Nonhuman Primates
Li S, Cai Z, Wu X, Holden D, Pracitto R, Kapinos M, Gao H, Labaree D, Nabulsi N, Carson RE, Huang Y. Synthesis and in Vivo Evaluation of a Novel PET Radiotracer for Imaging of Synaptic Vesicle Glycoprotein 2A (SV2A) in Nonhuman Primates. ACS Chemical Neuroscience 2018, 10: 1544-1554. PMID: 30396272, PMCID: PMC6810685, DOI: 10.1021/acschemneuro.8b00526.Peer-Reviewed Original ResearchConceptsSynaptic vesicle glycoprotein 2AStandardized uptake valuePET radiotracersNonhuman primatesAlterations of synapsesC-UCBPeak standardized uptake valueVivo evaluationHigh brain uptakeNovel PET radiotracersBrain uptakeSynaptic densityExcellent radiotracerPsychiatric disordersUptake valueCingulate cortexAlzheimer's diseaseBrain disordersNovel radiotracersRhesus monkeysNeurodegenerative diseasesTissue kineticsDiseaseAttractive imaging propertiesLevetiracetam
2017
PET Imaging Evaluation of Four σ1 Radiotracers in Nonhuman Primates
Baum E, Cai Z, Bois F, Holden D, Lin SF, Lara-Jaime T, Kapinos M, Chen Y, Deuther-Conrad W, Fischer S, Dukic-Stefanovic S, Bunse P, Wünsch B, Brust P, Jia H, Huang Y. PET Imaging Evaluation of Four σ1 Radiotracers in Nonhuman Primates. Journal Of Nuclear Medicine 2017, 58: 982-988. PMID: 28232607, DOI: 10.2967/jnumed.116.188052.Peer-Reviewed Original ResearchConceptsImaging evaluationHigh specific binding signalsRhesus monkeysFast tissue kineticsAdult male rhesus monkeysHigh brain uptakeMale rhesus monkeysBrain uptakeDistribution volume valuesBaseline scanRhesus brainVariety of diseasesSpecific binding signalsTime-activity curvesCingulate cortexAlzheimer's diseaseBrain regionsDistribution volumeRadiotracer bindingArterial input functionPET radiotracersPET tracersNonhuman primatesSame monkeysTissue kineticsThe Search for a Subtype-Selective PET Imaging Agent for the GABAA Receptor Complex: Evaluation of the Radiotracer [11C]ADO in Nonhuman Primates
Lin SF, Bois F, Holden D, Nabulsi N, Pracitto R, Gao H, Kapinos M, Teng JK, Shirali A, Ropchan J, Carson RE, Elmore CS, Vasdev N, Huang Y. The Search for a Subtype-Selective PET Imaging Agent for the GABAA Receptor Complex: Evaluation of the Radiotracer [11C]ADO in Nonhuman Primates. Molecular Imaging 2017, 16: 1536012117731258. PMID: 28929924, PMCID: PMC5912275, DOI: 10.1177/1536012117731258.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarbon RadioisotopesFemaleMacaca mulattaMalePositron-Emission TomographyPyrrolesQuinolonesRadiopharmaceuticalsReceptors, GABA-AConceptsNonhuman primatesNovel positron emission tomography (PET) radiotracerAbsolute test-retest variabilityFast tissue kineticsSubtype-selective GABATissue kineticsHigh brain uptakeGABAA receptor complexRegional binding potentialPositron emission tomography (PET) radiotracerPET imaging agentRegional distribution volumesTest-retest variabilityNondisplaceable volumeUndesirable side effectsRegion-specific distributionΓ-amino butyric acidAnticonvulsive effectBrain uptakeAnxiolytic effectsMinutes postinjectionOne-tissue compartment modelGABA sitesStriatal regionsRegional time-activity curves
2016
Comparative evaluation of two glycine transporter 1 radiotracers [11C]GSK931145 and [18F]MK‐6577 in baboons
Zheng MQ, Lin SF, Holden D, Naganawa M, Ropchan JR, Najafzaden S, Kapinos M, Tabriz M, Carson RE, Hamill TG, Huang Y. Comparative evaluation of two glycine transporter 1 radiotracers [11C]GSK931145 and [18F]MK‐6577 in baboons. Synapse 2016, 70: 112-120. PMID: 26671330, DOI: 10.1002/syn.21879.Peer-Reviewed Original ResearchAnimalsBenzamidesBrainBrain MappingCarbon RadioisotopesChromatography, High Pressure LiquidDrug Evaluation, PreclinicalFemaleGlycine AgentsGlycine Plasma Membrane Transport ProteinsKineticsLinear ModelsMagnetic Resonance ImagingMolecular StructurePapioPositron-Emission TomographyRadiopharmaceuticalsSulfonamides
2015
PET imaging evaluation of [18F]DBT-10, a novel radioligand specific to α7 nicotinic acetylcholine receptors, in nonhuman primates
Hillmer AT, Zheng MQ, Li S, Scheunemann M, Lin SF, Holden D, Labaree D, Ropchan J, Teodoro R, Deuther-Conrad W, Carson RE, Brust P, Huang Y. PET imaging evaluation of [18F]DBT-10, a novel radioligand specific to α7 nicotinic acetylcholine receptors, in nonhuman primates. European Journal Of Nuclear Medicine And Molecular Imaging 2015, 43: 537-547. PMID: 26455500, PMCID: PMC4733418, DOI: 10.1007/s00259-015-3209-0.Peer-Reviewed Original ResearchConceptsPurposePositron emission tomographyDose-dependent blockadeStandardized uptake valueΑ7 nicotinic acetylcholine receptorNonhuman primatesPeak standardized uptake valueBaseline PET scanParent fractionEx vivo analysisPlasma free fractionNicotinic acetylcholine receptorsTotal distribution volumeBrain tissue samplesRegional rank orderTwo-tissue compartment modelSpecific radioligandFrontal cortexOccipital cortexNovel radioligandPET scansArterial plasmaAcetylcholine receptorsUptake valueAlzheimer's diseaseBrain tissueMeasurement of Bmax and Kd with the Glycine Transporter 1 Radiotracer 18F-MK6577 using a Novel Multi-Infusion Paradigm
Xia Y, Zheng MQ, Holden D, Lin SF, Kapinos M, Ropchan J, Gallezot JD, Huang Y, Carson RE. Measurement of Bmax and Kd with the Glycine Transporter 1 Radiotracer 18F-MK6577 using a Novel Multi-Infusion Paradigm. Cerebrovascular And Brain Metabolism Reviews 2015, 35: 2001-2009. PMID: 26198176, PMCID: PMC4671121, DOI: 10.1038/jcbfm.2015.163.Peer-Reviewed Original ResearchConceptsGlycine transporter-1 inhibitorNew positron emission tomography radiotracerPositron emission tomography (PET) radiotracerPotential therapeutic agentNondisplaceable distribution volumeNMDA receptorsVivo affinityBaboon brainDistribution volumeBmax valuesTomography radiotracerTherapeutic agentsVivo KDBrainRank orderUnlabeled compoundsRadiotracerKdBrainstem
2014
Further evaluation of [11C]MP‐10 as a radiotracer for phosphodiesterase 10A: PET imaging study in rhesus monkeys and brain tissue metabolite analysis
Lin S, Labaree D, Chen M, Holden D, Gallezot J, Kapinos M, Teng J, Najafzadeh S, Plisson C, Rabiner EA, Gunn RN, Carson RE, Huang Y. Further evaluation of [11C]MP‐10 as a radiotracer for phosphodiesterase 10A: PET imaging study in rhesus monkeys and brain tissue metabolite analysis. Synapse 2014, 69: 86-95. PMID: 25450608, PMCID: PMC4275380, DOI: 10.1002/syn.21792.Peer-Reviewed Original ResearchConceptsRhesus monkeysPhosphodiesterase 10ASprague-Dawley ratsMP-10Dose-dependent mannerSpecific PET tracersHigh specific bindingPET imaging studiesTissue uptake kineticsBaseline scanBrain regionsImaging studiesFurther evaluationMultilinear analysis methodRegional volumesPET tracersNonhuman primatesPET imagingVivo studiesReference tissueMonkeysBrainCerebellumSpecific bindingPresent studyAn Improved Antagonist Radiotracer for the κ-Opioid Receptor: Synthesis and Characterization of 11C-LY2459989
Zheng MQ, Kim SJ, Holden D, Lin SF, Need A, Rash K, Barth V, Mitch C, Navarro A, Kapinos M, Maloney K, Ropchan J, Carson RE, Huang Y. An Improved Antagonist Radiotracer for the κ-Opioid Receptor: Synthesis and Characterization of 11C-LY2459989. Journal Of Nuclear Medicine 2014, 55: 1185-1191. PMID: 24854795, PMCID: PMC4826283, DOI: 10.2967/jnumed.114.138701.Peer-Reviewed Original ResearchConceptsHigh specific binding signalsΚ-opioid receptorsSpecific binding signalsPET radioligandRhesus monkeysPromising PET imaging agentSelective KOR antagonistNovel PET radioligandFavorable pharmacokinetic propertiesPET imaging agentMultilinear analysis-1 (MA1) methodAntagonist radiotracersKOR antagonistsPeripheral metabolismGlobus pallidusOpioid receptorsTracer candidatesFrontal cortexArterial input function measurementTemporal cortexCingulate cortexNeuropsychiatric diseasesPharmacokinetic propertiesFull antagonistHigh radiochemical purityIn Vivo Evaluation of 18F-MNI698: An 18F-Labeled Radiotracer for Imaging of Serotonin 4 Receptors in Brain
Tavares AA, Caillé F, Barret O, Papin C, Lee H, Morley TJ, Fowles K, Holden D, Seibyl JP, Alagille D, Tamagnan GD. In Vivo Evaluation of 18F-MNI698: An 18F-Labeled Radiotracer for Imaging of Serotonin 4 Receptors in Brain. Journal Of Nuclear Medicine 2014, 55: 858-864. PMID: 24686782, DOI: 10.2967/jnumed.113.132712.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainBrain MappingDioxanesDose-Response Relationship, RadiationFemaleFluorine RadioisotopesImage Processing, Computer-AssistedKineticsMacaca mulattaMalePiperidinesPositron-Emission TomographyRadiopharmaceuticalsReceptors, Serotonin, 5-HT4Reproducibility of ResultsSerotonin AntagonistsTime FactorsTissue DistributionConceptsBrain disordersPET radiotracersSerotonin 4 receptorBolus intravenous injectionNovel therapeutic approachesMultiple brain disordersAdult rhesus monkeysDifferent brain disordersDose limitDose-dependent mannerPromising PET radiotracerTest-retest variabilityTest-retest measurementsRadiotracer infusionBrain distributionBolus injectionIntravenous injectionArterial bloodTherapeutic approachesHuman studiesBody weightConstant infusionMonkey brainDistribution volumeInvasive methodWhole-body biodistribution and dosimetry estimates of a novel radiotracer for imaging of serotonin 4 receptors in brain: [18F]MNI-698
Tavares AA, Caillé F, Barret O, Papin C, Lee H, Morley TJ, Fowles K, Holden D, Seibyl JP, Alagille D, Tamagnan GD. Whole-body biodistribution and dosimetry estimates of a novel radiotracer for imaging of serotonin 4 receptors in brain: [18F]MNI-698. Nuclear Medicine And Biology 2014, 41: 432-439. PMID: 24674817, DOI: 10.1016/j.nucmedbio.2014.02.005.Peer-Reviewed Original ResearchConceptsSerotonin 4 receptorWhole-body biodistributionUrinary bladderDosimetry estimatesOLINDA/EXM 1.0 softwareNovel radiotracersEffective doseMSv/MBqIntravenous bolus injectionWhole-body positron emission tomography (PET) imagesHuman clinical trialsFuture clinical protocolsMain elimination routeAdult rhesus monkeysUrinary bladder modelWhole body weightClinical trialsBolus injectionClinical protocolsNew radiotracersRhesus monkeysCritical organsEffective dosesEmission tomography imagesBladder model