Daniel Holden
Research Associate Imaging Research CenterCards
About
Research
Publications
2026
High-resolution in utero SV2A PET imaging of the nonhuman primate brain using the NeuroEXPLORER.
Mehta S, Sun H, Micali N, Holden D, Fowles K, Rossano S, Zhang J, Ma C, Han P, Lee W, Duque A, Rakic P, Groman S, Carson R, Scheinost D, Toyonaga T. High-resolution in utero SV2A PET imaging of the nonhuman primate brain using the NeuroEXPLORER. Journal Of Cerebral Blood Flow And Metabolism : Official Journal Of The International Society Of Cerebral Blood Flow And Metabolism 2026, 271678x261429044. PMID: 41823342, PMCID: PMC12987752, DOI: 10.1177/0271678x261429044.Peer-Reviewed Original Research
2025
Characterization of [ 18 F]PF-NB1 Enantiomers for Imaging NMDA GluN2B Receptors in Nonhuman Primates and Comparison with Analogous 18 F‑labeled Radiotracers
Alluri S, Zheng M, Holden D, Ahmed H, Felchner Z, Kapinos M, Carson R, Ametamey S, Huang Y. Characterization of [ 18 F]PF-NB1 Enantiomers for Imaging NMDA GluN2B Receptors in Nonhuman Primates and Comparison with Analogous 18 F‑labeled Radiotracers. ACS Chemical Neuroscience 2025 PMID: 41392471, DOI: 10.1021/acschemneuro.5c00840.Peer-Reviewed Original ResearchVolume of distributionNondisplaceable volumeGluN2B expressionRegional volumesRegional volume of distributionNMDA GluN2B receptorBrain uptakeNondisplaceable binding potentialGluN2B-selective antagonistNonhuman primatesRegional time-activity curvesDynamic PET scansGlutamate-mediated excitotoxicityTime-activity curvesOne-tissue compartmentNeuropsychiatric disordersBrain regionsSelective antagonistGluN2B subunitGluN2B receptorsBinding potentialPET scansArterial input functionBlocking studiesSynaptic plasticityToward Imaging of the GABA Transporter Type 1 In Vivo: Quantitative Evaluation of 4 Novel PET Radiotracers in Nonhuman Primates
Gravel P, Gu J, Wang C, Volpi T, Gallezot J, Holden D, Fowles K, Zheng M, Zhang L, Borroni E, Honer M, Gobbi L, Tamagnan G, Huang Y, Carson R. Toward Imaging of the GABA Transporter Type 1 In Vivo: Quantitative Evaluation of 4 Novel PET Radiotracers in Nonhuman Primates. Journal Of Nuclear Medicine 2025, 66: 1652-1658. PMID: 40908122, PMCID: PMC12487869, DOI: 10.2967/jnumed.125.270332.Peer-Reviewed Original ResearchGABA transporter type 1Nonhuman primatesGAT-1Brain uptakeNondisplaceable binding potentialSubcortical gray matter regionsHuman studiesG-aminobutyric acidLow brain uptakeGray matter structuresLow specific bindingConclusion:Methods:Gray matter regionsType 1Results:Neuropsychiatric disordersPET radiotracersBinding potentialGABA signalingVolume of distributionMatter structuresRhesus monkeysBlock scanningGABA receptorsA novel approach for modeling in vivo enzyme turnover in the presence of a suicide inhibitor drug: A proof-of-concept brain PET study on MAG lipase
Volpi T, Holden D, Gallezot J, Nabulsi N, Lim K, Labaree D, Gao H, Kapinos M, Keliher E, Fonseca K, Trapa P, Varrone A, Halldin C, Maresca K, Huang Y, Carson R. A novel approach for modeling in vivo enzyme turnover in the presence of a suicide inhibitor drug: A proof-of-concept brain PET study on MAG lipase. Journal Of Cerebral Blood Flow And Metabolism : Official Journal Of The International Society Of Cerebral Blood Flow And Metabolism 2025, 45: 1947-1960. PMID: 40370302, PMCID: PMC12081407, DOI: 10.1177/0271678x251329254.Peer-Reviewed Original ResearchPET Imaging of Sphingosine-1-Phosphate Receptor 1 with [18F]TZ4877 in Nonhuman Primates
Gu J, Zheng M, Holden D, Fowles K, Qiu L, Felchner Z, Zhang L, Ropchan J, Gropler R, Carson R, Tu Z, Huang Y, Hillmer A. PET Imaging of Sphingosine-1-Phosphate Receptor 1 with [18F]TZ4877 in Nonhuman Primates. Molecular Imaging And Biology 2025, 27: 54-63. PMID: 39779653, PMCID: PMC12207061, DOI: 10.1007/s11307-024-01979-x.Peer-Reviewed Original ResearchConceptsSphingosine-1-phosphate receptor 1Absorbed radiation dose estimatesReceptor 1Nonhuman primatesFree fractionPlasma free fractionRadiation dose estimatesMetabolite-corrected input functionF-18 labeled radiotracersArterial blood samplesCritical organsPET/CT systemBolus injectionF-18Anesthetized nonhuman primatesDosimetry studiesHuman studiesDose estimatesVT/fPPET imaging dataS1PR1PET imagingInput functionBlood samplesPonesimod
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 ResearchConceptsAlzheimer'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 typesReceptorsChronic GCPII (glutamate‐carboxypeptidase‐II) inhibition reduces pT217Tau levels in the entorhinal and dorsolateral prefrontal cortices of aged macaques
Bathla S, Datta D, Liang F, Barthelemy N, Wiseman R, Slusher B, Asher J, Zeiss C, Ekanayake‐Alper D, Holden D, Terwilliger G, Duque A, Arellano J, van Dyck C, Bateman R, Xie Z, Nairn A, Arnsten A. Chronic GCPII (glutamate‐carboxypeptidase‐II) inhibition reduces pT217Tau levels in the entorhinal and dorsolateral prefrontal cortices of aged macaques. Alzheimer's & Dementia: Translational Research & Clinical Interventions 2023, 9: e12431. PMID: 37915375, PMCID: PMC10617575, DOI: 10.1002/trc2.12431.Peer-Reviewed Original ResearchSporadic Alzheimer's diseaseEntorhinal cortexGCPII inhibitionDorsolateral prefrontal cortexChronic inhibitionTau pathologyTau hyperphosphorylationAged macaquesType 3 metabotropic glutamate receptorAlzheimer's diseasePrefrontal cortexRhesus macaquesVehicle-treated monkeysAged rhesus macaquesMetabotropic glutamate receptorsApparent side effectsAmyloid beta 1Regulation of calciumGCPII inhibitorsKey etiological factorGCPII activityPrimate dlPFCNeuronal damageCSF analysisCalcium dysregulationPreclinical 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
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 Original Research