title: PET measurement of "GABA shift" in the rat brain: A preclinical application of bolus plus constant infusion paradigm of [18F]flumazenil.
abstract: We measured the tiagabine-induced enhancement of the GABAAreceptor's affinity for benzodiazepine ligands ("GABA shift") using [18F]flumazenil (FMZ) PET with preclinical application of bolus plus constant infusion (B/I). Differences in quantified results of [18F]FMZ binding were compared to that of [18F]FMZ PET with single bolus injection (SB).
  
  
  
  Sprague-Dawley rats underwent [18F]FMZ PET scans with B/I, which consisted of baseline and "GABA shift" sessions in a scan, or scans with SB one week apart. Tiagabine (10mg/kg) was intravenously injected after the baseline session. [18F]FMZ binding potentials (BPND) were calculated using an equilibrium ratio method and a modeling method for B/I and SB, respectively. Regional brain BPNDchanges (%) before and after the tiagabine treatment were also calculated.
  
  
  
  In PET studies with B/I (Kbol=20min), [18F]FMZ distribution in the various cortical and subcortical regions rapidly reached equilibrium. After the tiagabine treatment, [18F]FMZ BPNDwere substantially increased across the regions of interest (the frontal cortex, hippocampus, thalamus, and striatum), ranging from 3% to 7% BPNDchange (B/I) and 6-14% BPNDchange (SB), respectively. In PET studies with SB, a statistically significant increase of [18F]FMZ BPNDwas found only in the striatum, due to the greater inter-individual variance compared to those with B/I.
  
  
  
  Data demonstrated that an [18F]FMZ PET study with B/I (Kbol=20min) is both reliable and sensitive for the assessment of altered GABAAreceptor function induced by tiagabine treatment in the rat brain. These results may help to improve the efficiency of the development of new GABA-targeting drugs in the preclinical stage using [18F]FMZ PET.
authors.affiliation: Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, South Korea.
authors.forename: Wook
authors.initials: W
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam 463-707, South Korea; Advanced Institutes of Convergence Technology, 864-1, Iui-dong, Yeongtong-gu, Suwon 443-270, South Korea.
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Park
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam 463-707, South Korea.
authors.forename: Byung Seok
authors.initials: BS
authors.lastname: Moon
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam 463-707, South Korea; Advanced Institutes of Convergence Technology, 864-1, Iui-dong, Yeongtong-gu, Suwon 443-270, South Korea.
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Lee
authors.affiliation: Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, South Korea; Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam 463-707, South Korea; Advanced Institutes of Convergence Technology, 864-1, Iui-dong, Yeongtong-gu, Suwon 443-270, South Korea. Electronic address: kse@snu.ac.kr.
authors.forename: Sang Eun
authors.initials: SE
authors.lastname: Kim
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D005442:Flumazenil / Q000008:administration & dosage*; D005462:Fluorine Radioisotopes; D007267:Injections; D008297:Male; D049268:Positron-Emission Tomography; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*
chemical_list: D005462:Fluorine Radioisotopes; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D005442:Flumazenil
keywords: Bolus plus constant infusion; GABA shift; PET; [(18)F]flumazenil