Featured Publications
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 function
2024
An In Vivo High-Resolution Human Brain Atlas of Synaptic Density
Johansen A, Beliveau V, Colliander E, Raval N, Dam V, Gillings N, Aznar S, Svarer C, Plavén-Sigray P, Knudsen G. An In Vivo High-Resolution Human Brain Atlas of Synaptic Density. Journal Of Neuroscience 2024, 44: e1750232024. PMID: 38997157, PMCID: PMC11326867, DOI: 10.1523/jneurosci.1750-23.2024.Peer-Reviewed Original ResearchPathogenesis of brain disordersBrain disordersHuman brainFunctional topographySynaptic densityBrain physiologySynapse densityHigher-order cortical areasSynaptic vesicle glycoprotein 2AHuman brain physiologyHealthy human brainSV2A densityPET neuroimagingComparative neuroscienceNeuroscience researchCortical areasBrainAutoradiography dataDisordersNeuroscienceBrain atlasesHealthy humansSV2APositive associationMRNA patternsDevelopment of Peptide-Based Probes for Molecular Imaging of the Postsynaptic Density in the Brain
Fernandes E, Palner M, Raval N, Jeppesen T, Danková D, Bærentzen S, Werner C, Eilts J, Maric H, Doose S, Aripaka S, Kaalund S, Aznar S, Kjaer A, Schlosser A, Haugaard-Kedström L, Knudsen G, Herth M, Stro̷mgaard K. Development of Peptide-Based Probes for Molecular Imaging of the Postsynaptic Density in the Brain. Journal Of Medicinal Chemistry 2024, 67: 11975-11988. PMID: 38981131, DOI: 10.1021/acs.jmedchem.4c00615.Peer-Reviewed Original ResearchPostsynaptic densityBrain slicesPSD-95Tracer bindingPostsynaptic density protein 95Rat brain slicesMolecular imagingPost-mortem Parkinson's diseaseScaffold proteinQuantitative autoradiographyAbundant proteinsSynaptic transmissionPostsynaptic impairmentHigh-affinity inhibitorsSignaling moleculesImaging studiesFluorescent tagsCell imaging studiesSynaptic density patterns in early Alzheimer’s disease assessed by independent component analysis
Fang X, Raval N, O’Dell R, Naganawa M, Mecca A, Chen M, van Dyck C, Carson R. Synaptic density patterns in early Alzheimer’s disease assessed by independent component analysis. Brain Communications 2024, 6: fcae107. PMID: 38601916, PMCID: PMC11004947, DOI: 10.1093/braincomms/fcae107.Peer-Reviewed Original ResearchMedial temporal brain regionsAlzheimer's diseaseTemporal brain regionsCognitive deficitsBrain regionsCognitive impairmentPostmortem studiesBinds to SV2ASynaptic densityReduction of synaptic densityIndependent component analysisSynaptic lossAlzheimerDeficitsImpairmentBrainNeocortexComponent analysisPrimary pathologySV2AEvaluation of F-537-Tetrazine in a model for brain pretargeting imaging. Comparison to N-(3-[18F] fluoro-5-(1,2,4,5-tetrazin-3-yl)benzyl)propan-1-amine
Shalgunov V, van den Broek S, Andersen I, Raval N, Schäfer G, Barz M, Herth M, Battisti U. Evaluation of F-537-Tetrazine in a model for brain pretargeting imaging. Comparison to N-(3-[18F] fluoro-5-(1,2,4,5-tetrazin-3-yl)benzyl)propan-1-amine. Nuclear Medicine And Biology 2024, 128: 108877. PMID: 38232579, DOI: 10.1016/j.nucmedbio.2024.108877.Peer-Reviewed Original ResearchAn in vivo high-resolution human brain atlas of synaptic density
Johansen A, Beliveau V, Colliander E, Raval N, Dam V, Gillings N, Aznar S, Svarer C, Plaven-Sigray P, Knudsen G. An in vivo high-resolution human brain atlas of synaptic density. Neuroscience Applied 2024, 3: 104022. DOI: 10.1016/j.nsa.2024.104022.Peer-Reviewed Original Research
2023
Kinetic models for estimating occupancy from single-scan PET displacement studies
Laurell G, Plavén-Sigray P, Johansen A, Raval N, Nasser A, Madsen C, Madsen J, Hansen H, Donovan L, Knudsen G, Lammertsma A, Ogden R, Svarer C, Schain M. Kinetic models for estimating occupancy from single-scan PET displacement studies. Cerebrovascular And Brain Metabolism Reviews 2023, 43: 1544-1556. PMID: 37070382, PMCID: PMC10414003, DOI: 10.1177/0271678x231168591.Peer-Reviewed Original ResearchPretargeted imaging beyond the blood–brain barrier
Shalgunov V, van den Broek S, Andersen I, Vázquez R, Raval N, Palner M, Mori Y, Schäfer G, Herrmann B, Mikula H, Beschorner N, Nedergaard M, Syvänen S, Barz M, Knudsen G, Battisti U, Herth M. Pretargeted imaging beyond the blood–brain barrier. RSC Medicinal Chemistry 2023, 14: 444-453. PMID: 36970152, PMCID: PMC10034008, DOI: 10.1039/d2md00360k.Peer-Reviewed Original ResearchRational drug design approachDrug design approachBioorthogonal chemistryTetrazine ligationAttractive reactionPhysicochemical propertiesFluorine-18Blood-brain barrierLead compoundsMolecular imaging technologySoluble oligomersPositron emission tomographyBiomarker proteinsIdeal radionuclideTetrazineChemistryFavorable characteristicsDrug developmentOligomersPropertiesPretargetingNanomedicineCompoundsStructureReaction
2022
Positron Emission Tomography of Neuroimmune Responses in Humans: Insights and Intricacies
Raval NR, Wetherill RR, Wiers CE, Dubroff JG, Hillmer AT. Positron Emission Tomography of Neuroimmune Responses in Humans: Insights and Intricacies. Seminars In Nuclear Medicine 2022, 53: 213-229. PMID: 36270830, PMCID: PMC11261531, DOI: 10.1053/j.semnuclmed.2022.08.008.Peer-Reviewed Original Research In PressConceptsNeuroimmune targetsImmune systemNeuropsychiatric conditionsSphingosine-1-phosphate receptor 1Brain immune systemPurinergic P2X7 receptorVivo positron emission tomography (PET) imagingNitric oxide synthasePurinergic P2Y12 receptorPositron emission tomography (PET) imagingEmission Tomography ImagingPositron emission tomographyTranslocator protein 18Neuroimmune responsePET findingsNeuroimmune systemP2X7 receptorCyclooxygenase-2Oxide synthaseP2Y12 receptorPET resultsMonoamine oxidase BCyclooxygenase-1Colony-stimulating factor-1Receptor 1Evaluation of the α-synuclein PET radiotracer (d3)-[11C]MODAG-001 in pigs
Raval N, Madsen C, Shalgunov V, Nasser A, Battisti U, Beaman E, Juhl M, Jørgensen L, Herth M, Hansen H, Plavén-Sigray P, Knudsen G. Evaluation of the α-synuclein PET radiotracer (d3)-[11C]MODAG-001 in pigs. Nuclear Medicine And Biology 2022, 114: 42-48. PMID: 36095921, DOI: 10.1016/j.nucmedbio.2022.08.001.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseOccipital cortexΑ-synuclein pre-formed fibrilsInjected regionΑ-synuclein pathologyAD brain homogenatesDose-dependent effectPositron emission tomography (PET) radiotracerPre-formed fibrilsΑ-synuclein aggregatesReference regionAD homogenatesLogan graphical analysisLewy bodiesHistopathological hallmarksEarly diagnosisParkinson's diseasePET scansBrain homogenatesTime-activity curvesPig modelBrain regionsTomography radiotracerPig brainPET radiotracersAn in vivo Pig Model for Testing Novel Positron Emission Tomography Radioligands Targeting Cerebral Protein Aggregates
Raval NR, Nasser A, Madsen CA, Beschorner N, Beaman EE, Juhl M, Lehel S, Palner M, Svarer C, Plavén-Sigray P, Jørgensen LM, Knudsen GM. An in vivo Pig Model for Testing Novel Positron Emission Tomography Radioligands Targeting Cerebral Protein Aggregates. Frontiers In Neuroscience 2022, 16: 847074. PMID: 35368260, PMCID: PMC8966485, DOI: 10.3389/fnins.2022.847074.Peer-Reviewed Original ResearchPositron emission tomographyNovel radioligandPig modelAlzheimer's diseaseEmission tomographyΑ-synucleinGood translational modelΑ-synuclein pathologyBlood-brain barrierPostmortem human brain tissueReference tissue model 2Gadolinium-enhanced MRILarge animal modelNovel positron emission tomographyHuman brain tissueTimes higher uptakeCerebral injectionLewy bodiesVivo pig modelSaline injectionEssential clinical toolOccipital cortexParkinson's diseaseAppropriate radioligandsPET scansEvaluation of the α-synuclein PET radiotracer (d3)-[11C]MODAG-001 in a protein deposition pig model
Raval N, Shalgunov V, Nasser A, Madsen C, Battisti U, Herth M, Jørgensen L, Plavén-Sigray P, Knudsen G. Evaluation of the α-synuclein PET radiotracer (d3)-[11C]MODAG-001 in a protein deposition pig model. Neuroscience Applied 2022, 1: 100016. DOI: 10.1016/j.nsa.2022.100016.Peer-Reviewed Original Research
2021
Synaptic Density and Neuronal Metabolic Function Measured by Positron Emission Tomography in the Unilateral 6-OHDA Rat Model of Parkinson’s Disease
Raval NR, Gudmundsen F, Juhl M, Andersen IV, Speth N, Videbæk A, Petersen IN, Mikkelsen JD, Fisher PM, Herth MM, Plavén-Sigray P, Knudsen GM, Palner M. Synaptic Density and Neuronal Metabolic Function Measured by Positron Emission Tomography in the Unilateral 6-OHDA Rat Model of Parkinson’s Disease. Frontiers In Synaptic Neuroscience 2021, 13: 715811. PMID: 34867258, PMCID: PMC8636601, DOI: 10.3389/fnsyn.2021.715811.Peer-Reviewed Original ResearchNeuronal metabolic functionPositron emission tomographyParkinson's diseaseSynaptic densityCortical regionsJ bindingDopaminergic lesionVentral midbrainEmission tomographyIpsilateral ventral midbrainLower synaptic densityRostral substantia nigraUnilateral dopaminergic lesionNon-motor symptomsThalamo-cortical circuitsMetabolic functionsMedial forebrain bundleHigh synaptic densityMedial prefrontal cortexCerebral changesMotor dysfunctionUnilateral injectionDopaminergic neuronsSubstantia nigraBasal gangliaA Single Dose of Psilocybin Increases Synaptic Density and Decreases 5-HT2A Receptor Density in the Pig Brain
Raval NR, Johansen A, Donovan LL, Ros NF, Ozenne B, Hansen HD, Knudsen GM. A Single Dose of Psilocybin Increases Synaptic Density and Decreases 5-HT2A Receptor Density in the Pig Brain. International Journal Of Molecular Sciences 2021, 22: 835. PMID: 33467676, PMCID: PMC7830000, DOI: 10.3390/ijms22020835.Peer-Reviewed Original ResearchConceptsAntidepressive effectsR densitySingle dosePig brainSerotonin 2A receptor agonistSynaptic vesicle protein 2AAntidepressant effectsAntidepressive actionReceptor agonistAcute decreaseSynaptic densityReceptor densityCortex sectionsAwake pigsHippocampusDoseProtein 2ASynaptogenesisBrainPsilocybinPigsDaysAgonistsRadioligand
2020
Blocking of efflux transporters in rats improves translational validation of brain radioligands
Shalgunov V, Xiong M, L’Estrade E, Raval NR, Andersen IV, Edgar FG, Speth NR, Baerentzen SL, Hansen HD, Donovan LL, Nasser A, Peitersen ST, Kjaer A, Knudsen GM, Syvänen S, Palner M, Herth MM. Blocking of efflux transporters in rats improves translational validation of brain radioligands. EJNMMI Research 2020, 10: 124. PMID: 33074370, PMCID: PMC7572968, DOI: 10.1186/s13550-020-00718-x.Peer-Reviewed Original ResearchP-gp inhibitionBrain uptakePET tracersEfflux transportersDopamine D2/3 receptorsRat dataBackgroundPositron emission tomographyLow brain uptakeInitial preclinical evaluationD2/3 receptorsRat brainPreclinical evaluationMolecular imaging techniquesP-gpVivo pharmacologyEmission tomographyP-glycoproteinTranslational validationRodent dataPET radiotracersHigh expressionRatsDisease modelsTarget-specific bindingReceptorsThe radiosensitizer Onalespib increases complete remission in 177Lu-DOTATATE-treated mice bearing neuroendocrine tumor xenografts
Lundsten S, Spiegelberg D, Raval NR, Nestor M. The radiosensitizer Onalespib increases complete remission in 177Lu-DOTATATE-treated mice bearing neuroendocrine tumor xenografts. European Journal Of Nuclear Medicine And Molecular Imaging 2020, 47: 980-990. PMID: 31912256, PMCID: PMC7075859, DOI: 10.1007/s00259-019-04673-1.Peer-Reviewed Original ResearchConceptsComplete remissionToxicity profileNeuroendocrine tumorsSomatostatin receptorsCombination treatmentHistological analysisFavorable toxicity profileBetter therapeutic resultsDose-limiting organHeat shock protein 90 inhibitorShock protein 90 inhibitorsNeuroendocrine tumor xenograftsMonotherapy groupGlomerular injuryUnwanted side effectsCombination groupTherapeutic resultsTherapeutic effectTumor xenograftsSide effectsTumor uptakeRemissionXenograftsTumorsHSP70 upregulation