2023
Preclinical 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 trialsIn Vivo Imaging and Kinetic Modeling of Novel Glycogen Synthase Kinase-3 Radiotracers [11C]OCM-44 and [18F]OCM-50 in Non-Human Primates
Smart K, Zheng M, Holden D, Felchner Z, Zhang L, Han Y, Ropchan J, Carson R, Vasdev N, Huang Y. In Vivo Imaging and Kinetic Modeling of Novel Glycogen Synthase Kinase-3 Radiotracers [11C]OCM-44 and [18F]OCM-50 in Non-Human Primates. Pharmaceuticals 2023, 16: 194. PMID: 37259346, PMCID: PMC9959234, DOI: 10.3390/ph16020194.Peer-Reviewed Original ResearchPositron emission tomographyNon-human primatesMetabolite-corrected arterial input functionML/Free fractionWarrants further evaluationPotential therapeutic targetGood brain uptakeAdult rhesus macaquesPlasma free fractionArterial blood samplingGray matter regionsTwo-tissue compartment modelBrain uptakeRegional time-activity curvesBlood samplingPsychiatric disordersPET scansTherapeutic targetTime-activity curvesGray matterBrain regionsEmission tomographyFurther evaluationArterial input function
2022
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
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
2020
Dysregulation of Decision Making Related to Metabotropic Glutamate 5, but Not Midbrain D3, Receptor Availability Following Cocaine Self-administration in Rats
Groman SM, Hillmer AT, Liu H, Fowles K, Holden D, Morris ED, Lee D, Taylor JR. Dysregulation of Decision Making Related to Metabotropic Glutamate 5, but Not Midbrain D3, Receptor Availability Following Cocaine Self-administration in Rats. Biological Psychiatry 2020, 88: 777-787. PMID: 32826065, PMCID: PMC8935943, DOI: 10.1016/j.biopsych.2020.06.020.Peer-Reviewed Original ResearchConceptsCocaine-dependent individualsProbabilistic reversalRelapse-like behaviorTest of motivationReceptor availabilityPersistent drug useMetabotropic glutamate 5Neural mechanismsCompulsive patternsDecision-making processDrug-induced adaptationsSelective impairmentDrug useWeeks of abstinenceCocaine takingCocaine Self-AdministrationBrain regionsDegree of disruptionDays of cocaineAdult male ratsCocaine-induced increasesCocaine-induced changesDrug-induced alterationsRobust alterationsPositron emission tomographyPositron 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 Research
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 monkeys
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 kinetics
2016
Increased Nanoparticle Delivery to Brain Tumors by Autocatalytic Priming for Improved Treatment and Imaging
Han L, Kong DK, Zheng MQ, Murikinati S, Ma C, Yuan P, Li L, Tian D, Cai Q, Ye C, Holden D, Park JH, Gao X, Thomas JL, Grutzendler J, Carson RE, Huang Y, Piepmeier JM, Zhou J. Increased Nanoparticle Delivery to Brain Tumors by Autocatalytic Priming for Improved Treatment and Imaging. ACS Nano 2016, 10: 4209-4218. PMID: 26967254, PMCID: PMC5257033, DOI: 10.1021/acsnano.5b07573.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBiological TransportBlood-Brain BarrierBrain NeoplasmsCell Line, TumorDecanoic AcidsDrug Delivery SystemsEthanolaminesFemaleGenetic TherapyHeterograftsHumansMatrix Metalloproteinase 2MiceMice, Inbred C57BLNanoparticlesOptical ImagingPaclitaxelPermeabilityPolymersPurinesPyrazolesScorpion VenomsTranscytosisTumor MicroenvironmentConceptsBlood-brain barrierLow delivery efficiencyTransport of nanoparticlesCancer gene therapyNanoparticle deliveryMore nanoparticlesBrain tumorsNanoparticlesDelivery efficiencyGene therapySystemic deliveryNPsBrain malignanciesBBB modulatorsPharmacological agentsBrain cancerBrain regionsTumorsDeliveryBrainImproved treatmentInadequate amountsPositive feedback loopChemotherapyMalignancy
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 study