title: Imaging changes in glutamate transmission in vivo with the metabotropic glutamate receptor 5 tracer [11C] ABP688 and N-acetylcysteine challenge.
abstract: BACKGROUND
  An imaging method to probe glutamate levels in vivo would allow the study of glutamate transmission in disease states and in response to therapeutic interventions. Here we demonstrate the feasibility of this approach for the first time using positron emission tomography and [(11)C] ABP688, a radiotracer for an allosteric site on the metabotropic glutamate receptor 5.
  
  
  METHODS
  We conducted two sets of experiments in anesthetized baboons: test and retest without pharmacologic challenge and in combination with N-acetylcysteine (NAC), a promoter of the cystine-glutamate antiporter that increases extrasynaptic glutamate release. The goal was to assess whether NAC-induced changes in [(11)C] ABP688 binding potential, ΔBP(ND), could be detected above the noise in the measurement.
  
  
  RESULTS
  Linear mixed modeling comparing ΔBP(ND) from test-retest to ΔBP(ND) from NAC challenge across all brain regions showed a highly significant effect of treatment [F(1,40) = 21.2, p < .001]. ΔBP(ND) was significantly different from zero following NAC [F(1,20) = 76.6, p < .001] but not after test-retest studies.
  
  
  CONCLUSIONS
  NAC induced decrease in [(11)C] ABP688 ΔBP(ND) may be the result of allosteric modulation, although other mechanisms may be at play. We outline steps needed to replicate and validate this method as a new tool to measure in vivo glutamate transmission.
authors.affiliation: Department of Psychiatry, Columbia University, New York, New York; New York State Psychiatric Institute, New York, New York, USA. nobumiyake@marianna-u.ac.jp
authors.forename: Nobumi
authors.initials: N
authors.lastname: Miyake
authors.forename: Mette
authors.initials: M
authors.lastname: Skinbjerg
authors.forename: Balu
authors.initials: B
authors.lastname: Easwaramoorthy
authors.forename: Dileep
authors.initials: D
authors.lastname: Kumar
authors.forename: Ragy R
authors.initials: RR
authors.lastname: Girgis
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Xu
authors.forename: Mark
authors.initials: M
authors.lastname: Slifstein
authors.forename: Anissa
authors.initials: A
authors.lastname: Abi-Dargham
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D001931:Brain Mapping; D002250:Carbon Radioisotopes; D018698:Glutamic Acid / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D008297:Male; D010091:Oximes / Q000494:pharmacology; D010215:Papio; D011725:Pyridines / Q000494:pharmacology; D011877:Radionuclide Imaging; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D014018:Tissue Distribution
chemical_list: C510950:3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime; D002250:Carbon Radioisotopes; D010091:Oximes; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid; D000111:Acetylcysteine