Biological properties of 2′-[18F]fluoroflumazenil for central benzodiazepine receptor imaging

Chang, Young Soo; Jeong, Jae Min; Yoon, Young Il; Kang, Won Jun; Lee, Seung Jin; Lee, Dong Hoon; Chung, June Key; Lee, Myung Chul

doi:10.1016/j.nucmedbio.2004.12.004

Cited by 27 publications

(6 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the profile of synchronous power change in the prominent (β–γ) frequency range exhibits strong spatial similarities when compared with PET receptor occupancy studies (Fig. 6), where frontal, sensorimotor, temporal, and occipital cortices exhibit highest GABA A receptor binding [Chang et al, 2005; Fedi et al, 2006]. Here, we observe consistent changes across these regions, as discussed in further detail in the following sections.…”

Section: Discussionsupporting

confidence: 78%

“…Several studies have investigated the spatial distribution of benzodiazepine receptors, using autoradiography [Zezula et al, 1988], immunohistochemistry [Rudolph et al, 2001], or PET [Chang et al, 2005; Fedi et al, 2006]. Whilst these studies are able to determine the profile of binding across the cortex, their functional significance remains unclear.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Neuronal network pharmacodynamics of GABAergic modulation in the human cortex determined using pharmaco‐magnetoencephalography

Hall

Barnes

Furlong

et al. 2010

Human Brain Mapping

143

132

View full text Add to dashboard Cite

Neuronal network oscillations are a unifying phenomenon in neuroscience research, with comparable measurements across scales and species. Cortical oscillations are of central importance in the characterization of neuronal network function in health and disease and are influential in effective drug development. Whilst animal in vitro and in vivo electrophysiology is able to characterize pharmacologically induced modulations in neuronal activity, present human counterparts have spatial and temporal limitations. Consequently, the potential applications for a human equivalent are extensive. Here, we demonstrate a novel implementation of contemporary neuroimaging methods called pharmaco-magnetoencephalography. This approach determines the spatial profile of neuronal network oscillatory power change across the cortex following drug administration and reconstructs the time course of these modulations at focal regions of interest. As a proof of concept, we characterize the nonspecific GABAergic modulator diazepam, which has a broad range of therapeutic applications. We demonstrate that diazepam variously modulates θ (4–7 Hz), α (7–14 Hz), β (15–25 Hz), and γ (30–80 Hz) frequency oscillations in specific regions of the cortex, with a pharmacodynamic profile consistent with that of drug uptake. We examine the relevance of these results with regard to the spatial and temporal observations from other modalities and the various therapeutic consequences of diazepam and discuss the potential applications of such an approach in terms of drug development and translational neuroscience. Hum Brain Mapp, 2010. © 2009 Wiley-Liss, Inc.

show abstract

Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Neuronal network pharmacodynamics of GABAergic modulation in the human cortex determined using pharmaco‐magnetoencephalography

Hall

Barnes

Furlong

et al. 2010

Human Brain Mapping

143

132

View full text Add to dashboard Cite

show abstract

“…Firstly, [ 11 C] has a short radioactive half-life, thus requiring an onsite cyclotron and dose by dose production. To overcome this there has been a recent focus on developing [ 18 F]-radiolabelled FMZ conjugates, including [ 18 F]-FEFMZ, [ 18 F]-FFMZ and most recently [ 18 F]-FMZ [14], [15], [16]. [ 18 F] has a substantially longer half-life, meaning it does not need to be produced on site, and can therefore be used in a greater number of centres and is more practical for routine investigational use.…”

Section: Introductionmentioning

confidence: 99%

In Vivo Measurement of Hippocampal GABAA/cBZR Density with [18F]-Flumazenil PET for the Study of Disease Progression in an Animal Model of Temporal Lobe Epilepsy

et al. 2014

View full text Add to dashboard Cite

PurposeImbalance of inhibitory GABAergic neurotransmission has been proposed to play a role in the pathogenesis of temporal lobe epilepsy (TLE). This study aimed to investigate whether [18F]-flumazenil ([18F]-FMZ) PET could be used to non-invasively characterise GABAA/central benzodiazepine receptor (GABAA/cBZR) density and affinity in vivo in the post-kainic acid status epilepticus (SE) model of TLE.MethodsDynamic [18F]-FMZ -PET scans using a multi-injection protocol were acquired in four male wistar rats for validation of the partial saturation model (PSM). SE was induced in eight male Wistar rats (10 weeks of age) by i.p. injection of kainic acid (7.5–25 mg/kg), while control rats (n = 7) received saline injections. Five weeks post-SE, an anatomic MRI scan was acquired and the following week an [18F]-FMZ PET scan (3.6–4.6 nmol). The PET data was co-registered to the MRI and regions of interest drawn on the MRI for selected structures. A PSM was used to derive receptor density and apparent affinity from the [18F]-FMZ PET data.Key FindingsThe PSM was found to adequately model [18F]-FMZ binding in vivo. There was a significant decrease in hippocampal receptor density in the SE group (p<0.01), accompanied by an increase in apparent affinity (p<0.05) compared to controls. No change in cortical receptor binding was observed. Hippocampal volume reduction and cell loss was only seen in a subset of animals. Histological assessment of hippocampal cell loss was significantly correlated with hippocampal volume measured by MRI (p<0.05), but did not correlate with [18F]-FMZ binding.SignificanceAlterations to hippocampal GABAA/cBZR density and affinity in the post-kainic acid SE model of TLE are detectable in vivo with [18F]-FMZ PET and a PSM. These changes are independent from hippocampal cell and volume loss. [18F]-FMZ PET is useful for investigating the role that changes GABAA/cBZR density and binding affinity play in the pathogenesis of TLE.

show abstract

“…18 Ffluoroflumazenil was recently introduced for central benzodiazepine receptor imaging (14,15). However, it remains to be elucidated whether GABA-A receptor binding is increased within the ipsilateral motor cortex of the affected hemisphere or contralateral hemisphere after perinatal brain injury.…”

mentioning

confidence: 99%

Increased GABA-A Receptor Binding and Reduced Connectivity at the Motor Cortex in Children with Hemiplegic Cerebral Palsy: A Multimodal Investigation Using ¹⁸F-Fluoroflumazenil PET, Immunohistochemistry, and MR Imaging

Kim

Park

et al. 2013

J Nucl Med

View full text Add to dashboard Cite

Biological properties of 2′-[18F]fluoroflumazenil for central benzodiazepine receptor imaging

Cited by 27 publications

References 24 publications

Neuronal network pharmacodynamics of GABAergic modulation in the human cortex determined using pharmaco‐magnetoencephalography

Neuronal network pharmacodynamics of GABAergic modulation in the human cortex determined using pharmaco‐magnetoencephalography

In Vivo Measurement of Hippocampal GABAA/cBZR Density with [18F]-Flumazenil PET for the Study of Disease Progression in an Animal Model of Temporal Lobe Epilepsy

Increased GABA-A Receptor Binding and Reduced Connectivity at the Motor Cortex in Children with Hemiplegic Cerebral Palsy: A Multimodal Investigation Using ¹⁸F-Fluoroflumazenil PET, Immunohistochemistry, and MR Imaging

Contact Info

Product

Resources

About

Biological properties of 2′-[18F]fluoroflumazenil for central benzodiazepine receptor imaging

Cited by 27 publications

References 24 publications

Neuronal network pharmacodynamics of GABAergic modulation in the human cortex determined using pharmaco‐magnetoencephalography

Neuronal network pharmacodynamics of GABAergic modulation in the human cortex determined using pharmaco‐magnetoencephalography

In Vivo Measurement of Hippocampal GABAA/cBZR Density with [18F]-Flumazenil PET for the Study of Disease Progression in an Animal Model of Temporal Lobe Epilepsy

Increased GABA-A Receptor Binding and Reduced Connectivity at the Motor Cortex in Children with Hemiplegic Cerebral Palsy: A Multimodal Investigation Using 18F-Fluoroflumazenil PET, Immunohistochemistry, and MR Imaging

Contact Info

Product

Resources

About

Increased GABA-A Receptor Binding and Reduced Connectivity at the Motor Cortex in Children with Hemiplegic Cerebral Palsy: A Multimodal Investigation Using ¹⁸F-Fluoroflumazenil PET, Immunohistochemistry, and MR Imaging