title: Imaging synaptic density in the living human brain.
abstract: Chemical synapses are the predominant neuron-to-neuron contact in the central nervous system. Presynaptic boutons of neurons contain hundreds of vesicles filled with neurotransmitters, the diffusible signaling chemicals. Changes in the number of synapses are associated with numerous brain disorders, including Alzheimer's disease and epilepsy. However, all current approaches for measuring synaptic density in humans require brain tissue from autopsy or surgical resection. We report the use of the synaptic vesicle glycoprotein 2A (SV2A) radioligand [(11)C]UCB-J combined with positron emission tomography (PET) to quantify synaptic density in the living human brain. Validation studies in a baboon confirmed that SV2A is an alternative synaptic density marker to synaptophysin. First-in-human PET studies demonstrated that [(11)C]UCB-J had excellent imaging properties. Finally, we confirmed that PET imaging of SV2A was sensitive to synaptic loss in patients with temporal lobe epilepsy. Thus, [(11)C]UCB-J PET imaging is a promising approach for in vivo quantification of synaptic density with several potential applications in diagnosis and therapeutic monitoring of neurological and psychiatric disorders.
authors.affiliation: Yale Positron Emission Tomography Center, Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT 06520, USA. sjoerd.finnema@yale.edu.
authors.forename: Sjoerd J
authors.initials: SJ
authors.lastname: Finnema
authors.affiliation: Yale Positron Emission Tomography Center, Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT 06520, USA.
authors.forename: Nabeel B
authors.initials: NB
authors.lastname: Nabulsi
authors.affiliation: Department of Laboratory Medicine, Yale University, New Haven, CT 06520, USA.
authors.forename: Tore
authors.initials: T
authors.lastname: Eid
authors.affiliation: Department of Neurology, Yale University, New Haven, CT 06520, USA.
authors.forename: Kamil
authors.initials: K
authors.lastname: Detyniecki
authors.affiliation: Yale Positron Emission Tomography Center, Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT 06520, USA.
authors.forename: Shu-Fei
authors.initials: SF
authors.lastname: Lin
authors.affiliation: Yale Positron Emission Tomography Center, Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT 06520, USA.
authors.forename: Ming-Kai
authors.initials: MK
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine, Yale University, New Haven, CT 06520, USA.
authors.forename: Roni
authors.initials: R
authors.lastname: Dhaher
authors.affiliation: Yale Positron Emission Tomography Center, Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT 06520, USA.
authors.forename: David
authors.initials: D
authors.lastname: Matuskey
authors.affiliation: Yale Positron Emission Tomography Center, Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT 06520, USA.
authors.forename: Evan
authors.initials: E
authors.lastname: Baum
authors.affiliation: Yale Positron Emission Tomography Center, Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT 06520, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Holden
authors.affiliation: Department of Neurosurgery, Yale University, New Haven, CT 06520, USA.
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Spencer
authors.affiliation: UCB Pharma, B-1420 Braine-l'Alleud, Belgium.
authors.forename: Joël
authors.initials: J
authors.lastname: Mercier
authors.affiliation: UCB Pharma, B-1420 Braine-l'Alleud, Belgium.
authors.forename: Jonas
authors.initials: J
authors.lastname: Hannestad
authors.affiliation: Yale Positron Emission Tomography Center, Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT 06520, USA.
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Yale Positron Emission Tomography Center, Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT 06520, USA. Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging*; D004827:Epilepsy / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D049268:Positron-Emission Tomography; D013569:Synapses / Q000378:metabolism* / Q000473:pathology*
chemical_list: D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C076414:SV2A protein, human