2024
First-in-Human Study of 18F-SynVesT-2: An SV2A PET Imaging Probe with Fast Brain Kinetics and High Specific Binding
Drake L, Wu Y, Naganawa M, Asch R, Zheng C, Najafzadeh S, Pracitto R, Lindemann M, Li S, Ropchan J, Labaree D, Emery P, Dias M, Henry S, Nabulsi N, Matuskey D, Hillmer A, Gallezot J, Carson R, Cai Z, Huang Y. First-in-Human Study of 18F-SynVesT-2: An SV2A PET Imaging Probe with Fast Brain Kinetics and High Specific Binding. Journal Of Nuclear Medicine 2024, 65: jnumed.123.266470. PMID: 38360052, PMCID: PMC10924160, DOI: 10.2967/jnumed.123.266470.Peer-Reviewed Original ResearchFirst-in-human studyPlasma free fractionTime-activity curvesCentrum semiovaleNonhuman primate's resultsFirst-in-humanFree fractionNondisplaceable binding potentialRegional time-activity curvesLow nonspecific uptakeRegional distribution volumesHigh-resolution research tomograph scannerTest-retest reproducibilityCerebral blood flowSynaptic vesicle glycoprotein 2AHealthy volunteersArterial input functionNonspecific uptakePET imaging probeDistribution volumeSynapse densityIndividual MR imagesHighest specific bindingMR imagingPET imaging
2022
Drug characteristics derived from kinetic modeling: combined 11C-UCB-J human PET imaging with levetiracetam and brivaracetam occupancy of SV2A
Naganawa M, Gallezot J, Finnema S, Maguire R, Mercier J, Nabulsi N, Kervyn S, Henry S, Nicolas J, Huang Y, Chen M, Hannestad J, Klitgaard H, Stockis A, Carson R. Drug characteristics derived from kinetic modeling: combined 11C-UCB-J human PET imaging with levetiracetam and brivaracetam occupancy of SV2A. EJNMMI Research 2022, 12: 71. PMID: 36346513, PMCID: PMC9643320, DOI: 10.1186/s13550-022-00944-5.Peer-Reviewed Original ResearchTime-activity curvesBrain entryDrug concentrationsNon-human primate brainAnti-seizure activitySynaptic vesicle glycoprotein 2APlasma drug concentrationsPrevious human studiesBackgroundAntiepileptic drugsHealthy subjectsBlood samplesHuman studiesLevetiracetamPrimate brainEmission tomography dataBrivaracetamDistribution volumeArterial input functionBrainDrug characteristicsPositron emission tomography dataDrug entryFree fractionDrugsKinetic parameters k1
2016
Synthesis and Preclinical Evaluation of 11C-UCB-J as a PET Tracer for Imaging the Synaptic Vesicle Glycoprotein 2A in the Brain
Nabulsi N, Mercier J, Holden D, Carré S, Najafzadeh S, Vandergeten MC, Lin SF, Deo A, Price N, Wood M, Lara-Jaime T, Montel F, Laruelle M, Carson RE, Hannestad J, Huang Y. Synthesis and Preclinical Evaluation of 11C-UCB-J as a PET Tracer for Imaging the Synaptic Vesicle Glycoprotein 2A in the Brain. Journal Of Nuclear Medicine 2016, 57: 777-784. PMID: 26848175, DOI: 10.2967/jnumed.115.168179.Peer-Reviewed Original ResearchConceptsSynaptic vesicle glycoprotein 2AWhole-body biodistributionPET radiotracersNonhuman primatesDose-limiting organHigher free fractionGray matter regionsBaseline VTNondisplaceable distribution volumeAntiepileptic drugsVitro inhibition constantSynaptic densityPreclinical evaluationMonkey brainDistribution volumeArterial samplingEndocrine cellsRegional volumesMatter regionsRhesus macaquesPET tracersUCBFree fractionBrainTarget occupancy