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Abstract

INTRODUCTION:

We measured the tiagabine-induced enhancement of the GABAA receptor'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).

MATERIALS AND METHODS:

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 BPND changes (%) before and after the tiagabine treatment were also calculated.

RESULTS:

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 BPND were substantially increased across the regions of interest (the frontal cortex, hippocampus, thalamus, and striatum), ranging from 3% to 7% BPND change (B/I) and 6-14% BPND change (SB), respectively. In PET studies with SB, a statistically significant increase of [18F]FMZ BPND was found only in the striatum, due to the greater inter-individual variance compared to those with B/I.

CONCLUSIONS:

Data demonstrated that an [18F]FMZ PET study with B/I (Kbol=20min) is both reliable and sensitive for the assessment of altered GABAA receptor 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.

Author information

Kim W1, Park HS2, Moon BS3, Lee BC2, Kim SE4.​

1Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, South Korea.

2Department 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.

3Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam 463-707, South Korea.

4Department 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.