Yiyun Huang, PhD
Professor of Radiology and Biomedical ImagingCards
About
Research
Overview
The main focus of Dr. Henry Huang's research is the development of new and improved Positron Emission Tomography (PET) radioligands. PET ligand development is a process that involves the interplays of chemistry, biology, pharmacology and pharmacokinetics, and it requires a good understanding of all these scientific disciplines. Over the years Dr. Huang has been involved in the development of new or improved PET radioligands for the dopamine, serotonin, glutamate and acetylcholine receptors and transporters in the brain. Development of PET radioligands includes the following stages: 1. design and synthesis of candidate ligands; 2. in vitro pharmacological experiments to determine binding affinities and selectivity. 3. design and execution of biological and pharmacological experiments in live animals including rodents and non-human primates to evaluate the ligands’ in vivo pharmacology and pharmacokinetics such as distribution, binding selectivity and specificity, metabolism, clearance, and blood and brain kinetics; 4. determination of dosimetry and toxicology; 5. clinical trials to determine the ligands’ suitability for applications in humans to image targeted receptors, proteins, or enzymes.
PET imaging technique can be used to determine the concentrations of CNS receptors and transporters in discrete brain regions under normal conditions. It can also be used to probe the changes in the densities of certain receptors and transporters in diseases. Coupled with pharmacological manipulation or stimulation, PET imaging is capable of probing the abnormality in the neurotransmission system functions under diseased conditions. Further applications include determination of the receptor occupancy by marketed or experimental drugs and monitoring the outcome of drug treatment for diseases. In all these applications the key is the availability of an appropriate PET radioligand for a specific receptor, transporter, or enzyme. Therefore, development of PET radioligands is a critical component of PET imaging and will continue to be the major part of Dr. Huang's research. His current interest is the development of ligands for targets in the CNS encompassing many of the neurotransmission systems.
Publications
2024
Exploration of (R)-[11C]YH168 as a PET tracer for imaging monoacylglycerol lipase in the brain: from mice to non-human primates
He Y, Zheng M, Gu J, Reichert L, Trimborn J, Zhang H, Keller C, Crosby M, Collin L, Heer D, Pavlovic A, Topp A, Wittwer M, Grether U, Gobbi L, Schibli R, Huang Y, Mu L. Exploration of (R)-[11C]YH168 as a PET tracer for imaging monoacylglycerol lipase in the brain: from mice to non-human primates. European Journal Of Nuclear Medicine And Molecular Imaging 2024, 1-10. PMID: 39673602, DOI: 10.1007/s00259-024-07013-0.Peer-Reviewed Original ResearchMonoacylglycerol lipaseNon-human primatesIn vitro autoradiographyBrain regionsMice to non-human primatesMAGL knockoutNon-displaceable binding potentialRhesus monkeysNon-human primate brainRegional non-displaceable binding potentialsRegional time-activity curvesMouse brainCingulate cortexFrontal cortexEndocannabinoid systemLevels of radioactive uptakeMouse brain slicesOccipital cortexBrains of miceOne-tissue compartment modelBinding potentialMAGL expressionPET scansKnockout micePrimate brainPresynaptic terminal integrity is associated with glucose metabolism in Parkinson’s disease
Wang W, Wang Y, Xu L, Liu X, Hu Y, Li J, Huang Q, Ren S, Huang Y, Guan Y, Li Y, Hua F, Ye Q, Xie F. Presynaptic terminal integrity is associated with glucose metabolism in Parkinson’s disease. European Journal Of Nuclear Medicine And Molecular Imaging 2024, 1-10. PMID: 39572432, DOI: 10.1007/s00259-024-06993-3.Peer-Reviewed Original ResearchPositron emission tomographyDopamine transporterSynaptic densityGlucose metabolismDopamine transporter availabilityPD patientsPost-commissural caudateParkinson's diseaseReduced synaptic densityAssociated with glucose metabolismDopaminergic transporterMethodsA totalHealthy controlsSynaptic vesicle protein 2PatientsEmission tomographyCaudatePD groupMetabolic patternsTerminal integrityProtein 2DiseaseNC groupCaudate regionsMetabolismPlasma Glial Fibrillary Acid Protein and Phosphorated Tau 181 Association with Presynaptic Density-Dependent Tau Pathology at 18F-SynVesT-1 Brain PET Imaging.
Wu J, Li B, Wang J, Huang Q, Chen X, You Z, He K, Guo Q, Li S, Huang Y, Guo T, Dai W, Xiang W, Chen W, Yang D, Zhao J, Guan Y, Xie F, Wolfe S. Plasma Glial Fibrillary Acid Protein and Phosphorated Tau 181 Association with Presynaptic Density-Dependent Tau Pathology at 18F-SynVesT-1 Brain PET Imaging. Radiology 2024, 313: e233019. PMID: 39560478, PMCID: PMC11605102, DOI: 10.1148/radiol.233019.Peer-Reviewed Original ResearchConceptsP-tau-181Alzheimer's diseaseAD-related pathologyAmyloid-bPhosphor-tauTau pathologySynaptic densityTau accumulationSynaptic lossTauTau-PETDecreased synaptic densityGlial fibrillary acidic proteinPlasma glial fibrillary acidic proteinCortical thicknessAcidic proteinFibrillary acidic proteinRuijin HospitalProspective studyRelationship of plasmaBlood assayBlood markersPET/MRIBrain PET imagingPET imaging11C-UCB-J PET imaging is consistent with lower synaptic density in autistic adults
Matuskey D, Yang Y, Naganawa M, Koohsari S, Toyonaga T, Gravel P, Pittman B, Torres K, Pisani L, Finn C, Cramer-Benjamin S, Herman N, Rosenthal L, Franke C, Walicki B, Esterlis I, Skosnik P, Radhakrishnan R, Wolf J, Nabulsi N, Ropchan J, Huang Y, Carson R, Naples A, McPartland J. 11C-UCB-J PET imaging is consistent with lower synaptic density in autistic adults. Molecular Psychiatry 2024, 1-7. PMID: 39367053, DOI: 10.1038/s41380-024-02776-2.Peer-Reviewed Original ResearchPositron emission tomographySynaptic densityAutistic adultsBrain regionsAutistic featuresClinical phenotype of autismNon-autistic participantsPhenotype of autismNon-autistic individualsRelationship to clinical characteristicsSynaptic vesicle glycoprotein 2AAssociated with clinical measuresPost-mortem studiesPositron emission tomography scanPrefrontal cortexClinician ratingsAutism groupNeural basisBrain areasNeural processesBetween-group differencesVolumetric differencesBinding potentialDensity of synapsesAutismNovel 18F‑Labeled Benzimidazolone-Based Radioligands as Highly Selective Sigma‑2 Receptor Probes for Tumor Imaging
Wang J, Wang T, Mou T, Yang T, Gao X, An X, Hu B, Zhang J, Zhang X, Deuther-Conrad W, Huang Y, Jia H. Novel 18F‑Labeled Benzimidazolone-Based Radioligands as Highly Selective Sigma‑2 Receptor Probes for Tumor Imaging. Journal Of Medicinal Chemistry 2024, 67: 17392-17406. DOI: 10.1021/acs.jmedchem.4c01315.Peer-Reviewed Original ResearchSmall-animal PET/CTS2 receptorsAnimal PET/CTHigh subtype selectivityGlioma modelCo-administrationPET/CTLung cancerGlioma xenograftsBlocking studiesU87MG xenograftsA549 lung cancerCompound 4U87MG glioma xenograftsTumorTumor imagingReceptorsSubtype selectivityXenograftsRadiochemical yieldRadioligandSigma-2Active uptakeMolar activityU87MGValidation of a Simplified Tissue-to-Reference Ratio Measurement Using SUVR to Assess Synaptic Density Alterations in Alzheimer Disease with [11C]UCB-J PET
Young J, O’Dell R, Naganawa M, Toyonaga T, Chen M, Nabulsi N, Huang Y, Cooper E, Miller A, Lam J, Bates K, Ruan A, Nelsen K, Salardini E, Carson R, van Dyck C, Mecca A. Validation of a Simplified Tissue-to-Reference Ratio Measurement Using SUVR to Assess Synaptic Density Alterations in Alzheimer Disease with [11C]UCB-J PET. Journal Of Nuclear Medicine 2024, 65: jnumed.124.267419. PMID: 39299782, PMCID: PMC11533916, DOI: 10.2967/jnumed.124.267419.Peer-Reviewed Original ResearchDistribution volume ratioSUV ratioSynaptic densityEffect sizeAlzheimer's diseaseLongitudinal study of Alzheimer's diseaseMethods:</b> ParticipantsLongitudinal studyMeasure synaptic densityAD participantsStudy of Alzheimer's diseaseNormal cognitionReference regionOlder adultsMulticenterDensity alterationsClinical correlates of dopamine transporter availability in cross-sectional and longitudinal studies with [18F]FE-PE2I PET: independent validation with new insights
Honhar P, Sadabad F, Tinaz S, Gallezot J, Dias M, Naganawa M, Yang Y, Henry S, Hillmer A, Gao H, Najafzadeh S, Comley R, Nabulsi N, Huang Y, Finnema S, Carson R, Matuskey D. Clinical correlates of dopamine transporter availability in cross-sectional and longitudinal studies with [18F]FE-PE2I PET: independent validation with new insights. Brain Communications 2024, 6: fcae345. PMID: 39429243, PMCID: PMC11487911, DOI: 10.1093/braincomms/fcae345.Peer-Reviewed Original ResearchDAT availabilityMotor severitySubstantia nigraDopamine transporter availabilityClinical trials of Parkinson's diseaseParkinson's diseaseLongitudinal studyTracking longitudinal changesClinical correlatesVentral striatumTransporter availabilityNigrostriatal regionParkinson's disease patientsPutamenMotor severity scoresAssociated with increasesSubstantiaDATLongitudinal changesTremor scoreNegative associationNigraSubstantia nigra of Parkinson's disease patientsTremor severityPET biomarkersMicroglia-mediated neuroimmune suppression in PTSD is associated with anhedonia
Bonomi R, Hillmer A, Woodcock E, Bhatt S, Rusowicz A, Angarita G, Carson R, Davis M, Esterlis I, Nabulsi N, Huang Y, Krystal J, Pietrzak R, Cosgrove K. Microglia-mediated neuroimmune suppression in PTSD is associated with anhedonia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2406005121. PMID: 39172786, PMCID: PMC11363315, DOI: 10.1073/pnas.2406005121.Peer-Reviewed Original ResearchConceptsPTSD groupPrefrontal-limbic circuitsNeuroimmune responseAssociated with anhedoniaPosttraumatic stress disorderPositron emission tomography brain imagingTranslocator protein availabilityBrain immune functionAnhedonic symptomsStress disorderPeripheral immune dysfunctionPTSDGroup differencesSeverity of symptomsPsychiatric diseasesTranslocator proteinBrain imagingAdministration of lipopolysaccharideSymptomsMicroglial markersLPS-induced increaseCompared to controlsImmune functionSickness symptomsAnhedoniaNoninvasive quantification of [18F]SynVesT-1 binding using simplified reference tissue model 2
Naganawa M, Gallezot J, Li S, Nabulsi N, Henry S, Cai Z, Matuskey D, Huang Y, Carson R. Noninvasive quantification of [18F]SynVesT-1 binding using simplified reference tissue model 2. European Journal Of Nuclear Medicine And Molecular Imaging 2024, 52: 113-121. PMID: 39155309, DOI: 10.1007/s00259-024-06885-6.Peer-Reviewed Original ResearchPositron emission tomographyCentrum semiovaleReference regionPositron emission tomography scanTest-retest variabilityTest-retest reproducibilitySynaptic vesicle glycoprotein 2AOne-tissue compartmentArterial blood samplesRetest scansGold standardBrain uptakeEmission tomographyBlood samplesCerebellumNoninvasive quantificationSRTM2ConclusionOur findingsPopulation averageHealthy participantsMetabolite analysisScan timeBPNDSemiovaleLoss of synaptic density in nucleus basalis of meynert indicates distinct neurodegeneration in Alzheimer’s disease: the RJNB-D study
Li B, Chen H, Zheng Y, Xu X, You Z, Huang Q, Huang Y, Guan Y, Zhao J, Liu J, Xie F, Wang J, Xu W, Zhang J, Deng Y. Loss of synaptic density in nucleus basalis of meynert indicates distinct neurodegeneration in Alzheimer’s disease: the RJNB-D study. European Journal Of Nuclear Medicine And Molecular Imaging 2024, 52: 134-144. PMID: 39112615, DOI: 10.1007/s00259-024-06862-z.Peer-Reviewed Original ResearchWhite matter tractsCognitive impairmentSynaptic densityCognitive performancePositron emission tomographyNucleus basalisSeverity of cognitive impairmentAlzheimer's diseaseSynaptic lossNucleus basalis of MeynertBasalis of MeynertSynaptic vesicle glycoprotein 2Pathogenesis of Alzheimer's diseaseStandardized uptake value ratioCholinergic systemProfile of ADCN participantsPotential impairmentMMSE scoreMedial tractNBMImpairmentEmission tomographyLoss of synaptic densityNormal controls
Clinical Trials
Current Trials
HPA axis function in the brains of PTSD, Trauma Exposed, or Otherwise Healthy research participants utilizing PET and MRI imaging
HIC ID2000028748RoleSub InvestigatorPrimary Completion Date08/31/2025Recruiting ParticipantsGenderBothAge18 years - 55 yearsImaging the Dopamine Transporter in Parkinson's Disease
HIC ID2000023896RoleSub InvestigatorPrimary Completion Date12/31/2020Recruiting ParticipantsGenderBothAge40+ yearsImaging pancreatic beta-cells with PET neuroimaging agent 11C-PHNO
HIC ID2000021287RoleSub InvestigatorPrimary Completion Date07/31/2021Recruiting ParticipantsGenderBothAge18 years - 65 yearsSV2A PET Imaging in Healthy Subjects and Epilepsy Patients
HIC ID1603017469RoleSub InvestigatorPrimary Completion Date05/01/2024Recruiting ParticipantsGenderBothAge18 years - 90 years
Academic Achievements & Community Involvement
Get In Touch
Contacts
Email
Mailing Address
Radiology & Biomedical Imaging
PO Box 208048, Yale PET Center
New Haven, CT 06520-8048
United States