A5010488095- Nerve injury and regeneration
- Neuroinflammation and Neurodegeneration Mechanisms
- Tryptophan and brain disorders
- Neuroscience and Neuropharmacology Research
- Stress Responses and Cortisol
- Neuropeptides and Animal Physiology
- Alzheimer's disease research and treatments
- Epilepsy research and treatment
- Neurogenesis and neuroplasticity mechanisms
- Receptor Mechanisms and Signaling
- Pharmacological Effects and Toxicity Studies
- Parkinson's Disease Mechanisms and Treatments
- Immune Response and Inflammation
- Treatment of Major Depression
- Nicotinic Acetylcholine Receptors Study
- Neurotransmitter Receptor Influence on Behavior
- Functional Brain Connectivity Studies
- Immune cells in cancer
- Glioma Diagnosis and Treatment
- Medical Imaging Techniques and Applications
- Dementia and Cognitive Impairment Research
- Chemokine receptors and signaling
- Lanthanide and Transition Metal Complexes
- Alcoholism and Thiamine Deficiency
- Attention Deficit Hyperactivity Disorder
Karagozian & Case (United States)
2021
UCB Pharma (Belgium)
2012-2020
Yale University
2007-2020
Denali Therapeutics (United States)
2017
Chalmers University of Technology
2013
VA Connecticut Healthcare System
2012
Yale Cancer Center
2010
Icahn School of Medicine at Mount Sinai
2008
Sheba Medical Center
2008
University of Pisa
2008
Synaptic density in the living human brain was measured with positron emission tomography and a synaptic vesicle glycoprotein 2A tracer.
Significance Neuroinflammation is a brain immune response that associated with neurodegenerative diseases and primarily driven by activation of microglia, the brain’s resident macrophages. Dysfunctional microglial may contribute to behavioral changes observed in diseases. Upon activation, microglia express translocator protein, which can be imaged radiotracer [ 11 C]PBR28 positron emission tomography (PET) living human brain. We healthy subjects PET before after i.v. administration...
The synaptic vesicle glycoprotein 2A (SV2A) is found in secretory vesicles neurons and endocrine cells. PET with a selective SV2A radiotracer will allow characterization of drugs that modulate (e.g., antiepileptic drugs) potentially could be biomarker density neurodegenerative disorders). Here we describe the synthesis <sup>11</sup>C-UCB-J ((<i>R</i>)-1-((3-(<sup>11</sup>C-methyl-<sup>11</sup>C)pyridin-4-yl)methyl)-4-(3,4,5-trifluorophenyl)pyrrolidin-2-one) nonhuman primates, including...
Synaptic vesicle glycoprotein 2A (SV2A) is ubiquitously present in presynaptic terminals. Here we report kinetic modeling and test-retest reproducibility assessment of the SV2A positron emission tomography (PET) radioligand [11C]UCB-J humans. Five volunteers were examined twice on HRRT after bolus injection [11C]UCB-J. Arterial blood samples collected for measurements radiometabolites free fraction. Regional time-activity curves analyzed with 1-tissue (1T) 2-tissue (2T) compartment models to...
Summary Objective Rapid distribution to the brain is a prerequisite for antiepileptic drugs used treatment of acute seizures. The preclinical studies described here investigated high‐affinity synaptic vesicle glycoprotein 2A ( SV 2A) drug brivara‐cetam BRV ) its rate penetration and onset action. was compared with levetiracetam LEV ). Methods In vitro permeation were performed using Caco‐2 cells. Plasma levels measured over time after single oral dosing audiogenic mice correlated...
Lilly/Avid's AV-1451 is one of the most advanced tau PET tracers in clinic. Although results obtained Alzheimer's disease patients are compelling, discrimination tracer uptake healthy individuals and with supranuclear palsy (PSP) less clear as there substantial overlap signal multiple brain regions. Moreover, accurate quantification [18 F]AV-1451 may not be possible.The aim present study was to characterize vitro binding understand identify potential off-target that could explain poor...
Depression is associated with systemic inflammation, and the inflammation caused by endotoxin administration elicits mild depressive symptoms such as fatigue reduced interest. The neural correlates of that result from are poorly defined. aim this study was to use <sup>18</sup>F-FDG PET identify brain regions involved in response humans. <b>Methods:</b> Nine healthy subjects received double-blind (0.8 ng/kg) placebo on different days. used measure differences cerebral metabolic rate glucose...
The aim of this study was to radiolabel a novel bis-deuterium substituted l-deprenyl analog (fluorodeprenyl-D<sub>2</sub>) with <sup>18</sup>F and evaluate its potential visualize quantify monoamine oxidase (MAO) B activity in vivo. <b>Methods:</b> precursor compound (<b>5a</b> + <b>5b</b>) reference standard (<b>6</b>) were synthesized multistep syntheses. Recombinant human MAO-B MAO-A enzyme preparations used determine inhibitory concentrations 50%. Radiolabeling accomplished by...
Summary Objective Brivaracetam (BRV) and levetiracetam (LEV) are antiepileptic drugs that bind synaptic vesicle glycoprotein 2A (SV2A). In vitro in vivo animal studies suggest faster brain penetration SV2A occupancy (SO) after dosing with BRV than LEV. We evaluated human SO time course of LEV at therapeutically relevant doses using the positron emission tomography (PET) tracer 11 C‐UCB‐J ( EP0074 ; NCT02602860 ). Methods Healthy volunteers were recruited into three cohorts. Cohort 1 (n = 4)...
Abstract Structural neuroimaging studies have provided evidence of differences in local brain volume between cocaine‐dependent and healthy control individuals. While sex aetiology, course dysfunction associated with chronic cocaine abuse been previously documented, sex‐specific has not examined thus far. This study sex‐related grey matter subjects using voxel‐based morphometry. High‐resolution T 1 structural scans were obtained from 36 inpatient, treatment‐engaged 3‐week abstinent ( CD )...