2023
Imaging the brain’s immune response to alcohol with [11C]PBR28 TSPO Positron Emission Tomography
Raval N, Angarita G, Matuskey D, Miller R, Drake L, Kapinos M, Nabulsi N, Huang Y, Carson R, O’Malley S, Cosgrove K, Hillmer A. Imaging the brain’s immune response to alcohol with [11C]PBR28 TSPO Positron Emission Tomography. Molecular Psychiatry 2023, 28: 3384-3390. PMID: 37532797, PMCID: PMC10743097, DOI: 10.1038/s41380-023-02198-6.Peer-Reviewed Original ResearchConceptsVolume of distributionBlood alcohol levelsPositron emission tomographyBrain immune responseImmune responseAlcohol challengeEmission tomographyPeak blood alcohol levelsMultilinear analysis 1Peripheral immune functionVivo human evidenceLaboratory alcohol challengeTSPO positron emission tomographyBinge levelsPlasma cytokinesImmune dysfunctionNeuroimmune systemIL-6MCP-1Cytokines TNFAcute effectsScan dayArterial bloodHuman evidenceImmune functionPreclinical 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 trialsCholinergic system adaptations are associated with cognitive function in people recently abstinent from smoking: a (-)-[18F]flubatine PET study
Calakos K, Hillmer A, Anderson J, LeVasseur B, Baldassarri S, Angarita G, Matuskey D, Kapinos M, Zheng M, Huang Y, Cosgrove K. Cholinergic system adaptations are associated with cognitive function in people recently abstinent from smoking: a (-)-[18F]flubatine PET study. Neuropsychopharmacology 2023, 48: 683-689. PMID: 36681758, PMCID: PMC9938267, DOI: 10.1038/s41386-023-01535-1.Peer-Reviewed Original ResearchConceptsExecutive functionCholinergic systemWorse executive functionAcetylcholine levelsVerbal learningCognitive batteryPositron emission tomography brainCognitive dataAbstinent smokersCognitive functionCognitive deficitsCortical acetylcholine levelsEarly smoking cessationAcetylcholinesterase inhibitor physostigmineCognitionQuit attemptsNAChR sitesPhysostigmine administrationTomography brainSmoking statusSmoking cessationInhibitor physostigmineTreatment strategiesAgonist radioligandPhysostigmine challenge
2022
First-in-human evaluation of 18F-BMS-986327 as a novel PET tracer to assess lysophosphatidic acid receptor 1 (LPA1) target engagement in the lung
Smith R, Donnelly D, Gallezot J, Lu Y, Murphy B, Cheng P, Kim J, Charles E, Du S, Holden D, Najafzadeh S, Gao H, Kapinos M, Ropchan J, Nabulsi N, Huang H, Fischer A, Carson R. First-in-human evaluation of 18F-BMS-986327 as a novel PET tracer to assess lysophosphatidic acid receptor 1 (LPA1) target engagement in the lung. 2022, 1164. DOI: 10.1183/13993003.congress-2022.1164.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsP-304 The synthesis and bioevaluation of a novel and brain penetrable PARP1 tracer [18F]Pamiparib in rodents and nonhuman primates
Tong J, Chen B, Gu J, Alluri S, Zheng M, Zheng C, Felchner Z, Gao H, Zhang L, Kapinos M, Labaree D, Ropchan J, Nabulsi N, Carson R, Huang Y, Cai Z. P-304 The synthesis and bioevaluation of a novel and brain penetrable PARP1 tracer [18F]Pamiparib in rodents and nonhuman primates. Nuclear Medicine And Biology 2022, 108: s214-s215. DOI: 10.1016/s0969-8051(22)00440-1.Peer-Reviewed Original ResearchP-303 Synthesis and preclinical evaluation of PD-L1 PET tracer [18F]FDHPA in mice
Tong J, Chen B, Alluri S, Gu J, Zheng M, Zheng C, Felchner Z, Gao H, Zhang L, Kapinos M, Labaree D, Ropchan J, Nabulsi N, Marquez-Nostra B, Carson R, Huang Y, Cai Z. P-303 Synthesis and preclinical evaluation of PD-L1 PET tracer [18F]FDHPA in mice. Nuclear Medicine And Biology 2022, 108: s214. DOI: 10.1016/s0969-8051(22)00439-5.Peer-Reviewed Original ResearchComparison 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 ResearchConceptsNon-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
Imaging brain cortisol regulation in PTSD with a target for 11β-hydroxysteroid dehydrogenase type 1
Bhatt S, Hillmer AT, Rusowicz A, Nabulsi N, Matuskey D, Angarita GA, Najafzadeh S, Kapinos M, Southwick SM, Krystal JH, Carson RE, Huang Y, Cosgrove KP. Imaging brain cortisol regulation in PTSD with a target for 11β-hydroxysteroid dehydrogenase type 1. Journal Of Clinical Investigation 2021, 131: e150452. PMID: 34651587, PMCID: PMC8516462, DOI: 10.1172/jci150452.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderPositron emission tomographyVolume of distributionDehydrogenase type 1Trauma-exposed controlsPTSD groupTranslocator proteinType 1Veterans Affairs (VA) National CenterOverall PTSD severityBrain glucocorticoidBrain immuneMethodsSixteen individualsPeripheral cortisolMicroglial markersImmune suppressionTranslational Science AwardsCortisol levelsNIH National CenterTC groupCortisol regulationEmission tomographyStress disorderLower PTSD symptomsPTSD symptoms
2020
First-in-Human Evaluation of 18F-SynVesT-1, a Radioligand for PET Imaging of Synaptic Vesicle Glycoprotein 2A
Naganawa M, Li S, Nabulsi N, Henry S, Zheng MQ, Pracitto R, Cai Z, Gao H, Kapinos M, Labaree D, Matuskey D, Huang Y, Carson RE. First-in-Human Evaluation of 18F-SynVesT-1, a Radioligand for PET Imaging of Synaptic Vesicle Glycoprotein 2A. Journal Of Nuclear Medicine 2020, 62: 561-567. PMID: 32859701, PMCID: PMC8049363, DOI: 10.2967/jnumed.120.249144.Peer-Reviewed Original ResearchConceptsC-UCBSynaptic densityRegional time-activity curvesTime-activity curvesDistribution volumeMetabolite-corrected arterial input functionPET imagingMultilinear analysis 1Synaptic vesicle glycoprotein 2AAntiepileptic drug levetiracetamTotal distribution volumeNondisplaceable distribution volumeCentrum semiovaleBlocking doseHealthy volunteersHuman studiesDrug levetiracetamLassen plotNeuropsychiatric disordersPET radioligandArterial input functionNonhuman primatesLevetiracetamReference regionRadioligandFeasibility study of PET dynamic imaging of [18F]DHMT for quantification of reactive oxygen species in the myocardium of large animals
Wu J, Boutagy NE, Cai Z, Lin SF, Zheng MQ, Feher A, Stendahl JC, Kapinos M, Gallezot JD, Liu H, Mulnix T, Zhang W, Lindemann M, Teng JK, Miller EJ, Huang Y, Carson RE, Sinusas AJ, Liu C. Feasibility study of PET dynamic imaging of [18F]DHMT for quantification of reactive oxygen species in the myocardium of large animals. Journal Of Nuclear Cardiology 2020, 29: 216-225. PMID: 32415628, PMCID: PMC7666654, DOI: 10.1007/s12350-020-02184-3.Peer-Reviewed Original ResearchPTSD is associated with neuroimmune suppression: evidence from PET imaging and postmortem transcriptomic studies
Bhatt S, Hillmer AT, Girgenti MJ, Rusowicz A, Kapinos M, Nabulsi N, Huang Y, Matuskey D, Angarita GA, Esterlis I, Davis MT, Southwick SM, Friedman MJ, Duman R, Carson R, Krystal J, Pietrzak R, Cosgrove K. PTSD is associated with neuroimmune suppression: evidence from PET imaging and postmortem transcriptomic studies. Nature Communications 2020, 11: 2360. PMID: 32398677, PMCID: PMC7217830, DOI: 10.1038/s41467-020-15930-5.Peer-Reviewed Original ResearchMeSH KeywordsAcetamidesAdaptor Proteins, Signal TransducingAdultBrainCase-Control StudiesFemaleGene Expression ProfilingHealthy VolunteersHumansMaleMicrogliaMiddle AgedPositron-Emission TomographyPyridinesRadiopharmaceuticalsReceptors, GABAReceptors, Tumor Necrosis Factor, Member 14Sex FactorsStress Disorders, Post-TraumaticYoung AdultConceptsPosttraumatic stress disorderPeripheral immune activationImmune activationHigher C-reactive protein levelsC-reactive protein levelsTSPO availabilityTranslocator proteinBrain microglial activationTomography brain imagingStress-related pathophysiologyPositron emission tomography (PET) brain imagingNeuroimmune activationMicroglial activationPTSD symptom severityImmunologic regulationPostmortem studiesPTSD subgroupHealthy individualsSymptom severityTrauma exposurePTSD groupStress disorderLower relative expressionBrain imagingPET imagingPositron 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 ResearchBody Mass Index and Age Effects on Brain 11β-Hydroxysteroid Dehydrogenase Type 1: a Positron Emission Tomography Study
Bini J, Bhatt S, Hillmer AT, Gallezot JD, Nabulsi N, Pracitto R, Labaree D, Kapinos M, Ropchan J, Matuskey D, Sherwin RS, Jastreboff AM, Carson RE, Cosgrove K, Huang Y. Body Mass Index and Age Effects on Brain 11β-Hydroxysteroid Dehydrogenase Type 1: a Positron Emission Tomography Study. Molecular Imaging And Biology 2020, 22: 1124-1131. PMID: 32133575, PMCID: PMC7351613, DOI: 10.1007/s11307-020-01490-z.Peer-Reviewed Original ResearchConceptsBody mass indexPositron emission tomographyDehydrogenase type 1Mass indexObese individualsEnzyme 11β-hydroxysteroid dehydrogenase type 1Whole brainType 1Higher body mass indexPositron emission tomography studyVT valuesSevere Alzheimer's diseaseEmission tomography studiesSteroid stress hormonesAge-associated increaseMean whole brainSignificant age-associated increaseRegional distribution volumesVisceral adiposityInsulin resistanceActive cortisolExcess cortisolInactive cortisoneMemory dysfunctionParietal lobe
2019
The Kappa Opioid Receptor Is Associated With Naltrexone-Induced Reduction of Drinking and Craving
de Laat B, Goldberg A, Shi J, Tetrault JM, Nabulsi N, Zheng MQ, Najafzadeh S, Gao H, Kapinos M, Ropchan J, O'Malley SS, Huang Y, Morris ED, Krishnan-Sarin S. The Kappa Opioid Receptor Is Associated With Naltrexone-Induced Reduction of Drinking and Craving. Biological Psychiatry 2019, 86: 864-871. PMID: 31399255, DOI: 10.1016/j.biopsych.2019.05.021.Peer-Reviewed Original ResearchConceptsKappa-opioid receptorsAlcohol use disorderOpioid receptorsUse disordersNonselective opioid receptor antagonistModest clinical effectsEfficacy of naltrexoneOpioid receptor antagonistDSM-IV criteriaPositron emission tomographyAlcohol Urge QuestionnaireNaltrexone initiationNaltrexone therapyClinical effectsReceptor antagonistTherapeutic effectCingulate cortexDrinking paradigmHeavy drinkersBilateral insulaNaltrexoneAlcohol dependenceBrain regionsEmission tomographyPrefrontal cortexFirst in-human PET study and kinetic evaluation of [18F]AS2471907 for imaging 11β-hydroxysteroid dehydrogenase type 1
Bhatt S, Nabulsi NB, Li S, Cai Z, Matuskey D, Bini J, Najafzadeh S, Kapinos M, Ropchan JR, Carson RE, Cosgrove KP, Huang Y, Hillmer AT. First in-human PET study and kinetic evaluation of [18F]AS2471907 for imaging 11β-hydroxysteroid dehydrogenase type 1. Cerebrovascular And Brain Metabolism Reviews 2019, 40: 695-704. PMID: 30895878, PMCID: PMC7168798, DOI: 10.1177/0271678x19838633.Peer-Reviewed Original ResearchImaging the Enzyme 11β-Hydroxysteroid Dehydrogenase Type 1 with PET: Evaluation of the Novel Radiotracer 11C-AS2471907 in Human Brain
Gallezot JD, Nabulsi N, Henry S, Pracitto R, Planeta B, Ropchan J, Lin SF, Labaree D, Kapinos M, Shirali A, Lara-Jaime T, Gao H, Matuskey D, Walzer M, Marek GJ, Bellaire S, Yuan N, Carson RE, Huang Y. Imaging the Enzyme 11β-Hydroxysteroid Dehydrogenase Type 1 with PET: Evaluation of the Novel Radiotracer 11C-AS2471907 in Human Brain. Journal Of Nuclear Medicine 2019, 60: 1140-1146. PMID: 30877174, DOI: 10.2967/jnumed.118.219766.Peer-Reviewed Original ResearchConceptsTest-retest variabilityNondisplaceable distribution volumeOccipital cortexEnzyme 11β-hydroxysteroid dehydrogenase type 1White matterDistribution volumeTreatment of depressionDehydrogenase type 1Large cortical regionsPosttraumatic stress disorderHuman brainAdditional scansIntraclass correlation coefficientAge-related cognitive functionBolus administrationFrontal cortexCaudate nucleusAdipose tissueTime-activity curvesNovel radiotracersGlucocorticoid levelsParietal cortexCortical regionsPattern of uptakeType 1Development 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 ResearchConceptsMultilinear 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
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
Novel 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