title: In vivo ketamine-induced changes in [¹¹C]ABP688 binding to metabotropic glutamate receptor subtype 5.
abstract: BACKGROUND
  At subanesthetic doses, ketamine, an N-methyl-D-aspartate glutamate receptor antagonist, increases glutamate release. We imaged the acute effect of ketamine on brain metabotropic glutamatergic receptor subtype 5 with a high-affinity positron emission tomography (PET) ligand [(11)C]ABP688 (E)-3-[2-(6-methyl-2-pyridinyl)ethynyl]-2-cyclohexen-1-one-O-(methyl-11C)oxime, a negative allosteric modulator of the metabotropic glutamatergic receptor subtype 5.
  
  
  METHODS
  Two [(11)C]ABP688 PET scans were performed in 10 healthy nonsmoking human volunteers (34 ± 13 years old); the two PET scans were performed on the same day-before (scan 1) and during intravenous ketamine administration (.23 mg/kg over 1 min, then .58 mg/kg over 1 hour; scan 2). The PET data were acquired for 90 min immediately after [(11)C]ABP688 bolus injection. Input functions were obtained through arterial blood sampling with metabolite analysis.
  
  
  RESULTS
  A significant reduction in [(11)C]ABP688 volume of distribution was observed in scan 2 relative to scan 1 of 21.3% ± 21.4%, on average, in the anterior cingulate, medial prefrontal cortex, orbital prefrontal cortex, ventral striatum, parietal lobe, dorsal putamen, dorsal caudate, amygdala, and hippocampus. There was a significant increase in measurements of dissociative state after ketamine initiation (p < .05), which resolved after completion of the scan.
  
  
  CONCLUSIONS
  This study provides first evidence that ketamine administration decreases [(11)C]ABP688 binding in vivo in human subjects. The results suggest that [(11)C]ABP688 binding is sensitive to ketamine-induced effects, although the high individual variation in ketamine response requires further examination.
authors.affiliation: Departments of Psychiatry, Stony Brook University, Stony Brook, New York, New York; Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York, New York. Electronic address: Christine.DeLorenzo@stonybrookmedicine.edu.
authors.forename: Christine
authors.initials: C
authors.lastname: DeLorenzo
authors.affiliation: Department of Psychiatry, Columbia University, New York, New York.
authors.forename: Nicole
authors.initials: N
authors.lastname: DellaGioia
authors.affiliation: Department of Psychiatry, Columbia University, New York, New York; Departments of Biomedical Engineering, Yale University, New Haven; Child Study Center, Yale University, New Haven.
authors.forename: Michael
authors.initials: M
authors.lastname: Bloch
authors.affiliation: Department of Psychiatry, Columbia University, New York, New York.
authors.forename: Gerard
authors.initials: G
authors.lastname: Sanacora
authors.affiliation: Departments of Psychiatry, Yale University, New Haven.
authors.forename: Nabeel
authors.initials: N
authors.lastname: Nabulsi
authors.affiliation: Department of Psychiatry, Columbia University, New York, New York; Departments of Biomedical Engineering, Yale University, New Haven; Clinical Neuroscience Division, National Center for PTSD, West Haven, Connecticut.
authors.forename: Chadi
authors.initials: C
authors.lastname: Abdallah
authors.affiliation: Departments of Radiology, Stony Brook University, Stony Brook, New York, New York.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Departments of Preventive Medicine, Stony Brook University, Stony Brook, New York, New York.
authors.forename: Ruofeng
authors.initials: R
authors.lastname: Wen
authors.affiliation: Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York, New York.
authors.forename: J John
authors.initials: JJ
authors.lastname: Mann
authors.affiliation: Department of Psychiatry, Columbia University, New York, New York; Departments of Biomedical Engineering, Yale University, New Haven; Clinical Neuroscience Division, National Center for PTSD, West Haven, Connecticut.
authors.forename: John H
authors.initials: JH
authors.lastname: Krystal
authors.affiliation: Departments of Biomedical Engineering, Stony Brook University, Stony Brook, New York, New York.
authors.forename: Ramin V
authors.initials: RV
authors.lastname: Parsey
authors.affiliation: Departments of Psychiatry, Yale University, New Haven; Diagnostic Radiology, Yale University, New Haven.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
authors.affiliation: Department of Psychiatry, Columbia University, New York, New York; Departments of Biomedical Engineering, Yale University, New Haven; Child Study Center, Yale University, New Haven.
authors.forename: Irina
authors.initials: I
authors.lastname: Esterlis
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D001931:Brain Mapping; D002250:Carbon Radioisotopes; D018691:Excitatory Amino Acid Antagonists / Q000097:blood / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007649:Ketamine / Q000097:blood / Q000494:pharmacology*; D008606:Mental Processes / Q000187:drug effects; D009483:Neuropsychological Tests; D010091:Oximes; D049268:Positron-Emission Tomography; D011725:Pyridines; D019275:Radiopharmaceuticals; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism*
chemical_list: C510950:3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime; D002250:Carbon Radioisotopes; D018691:Excitatory Amino Acid Antagonists; D010091:Oximes; D011725:Pyridines; D019275:Radiopharmaceuticals; D064529:Receptor, Metabotropic Glutamate 5; D007649:Ketamine
keywords: Brain; Glutamate; Ketamine; PET; [(11)C]ABP688; mGluR5