Improved work-up procedure for the production of [18F]flumazenil and first results of its use with a high-resolution research tomograph in human stroke

Recent imaging studies have demonstrated that levels of resting γ-aminobutyric acid (GABA) in the visual cortex predict the degree of stimulus-induced activity in the same region. These studies have used the presentation of discrete visual stimulus; the change from closed eyes to open also represents a simple visual stimulus, however, and has been shown to induce changes in local brain activity and in functional connectivity between regions. We thus aimed to investigate the role of the GABA system, specifically GABAA receptors, in the changes in brain activity between the eyes closed (EC) and eyes open (EO) state in order to provide detail at the receptor level to complement previous studies of GABA concentrations. We conducted an fMRI study involving two different modes of the change from EC to EO: an EO and EC block design, allowing the modeling of the haemodynamic response, followed by longer periods of EC and EO to allow the measuring of functional connectivity. The same subjects also underwent [18F]Flumazenil PET to measure GABAA receptor binding potentials. It was demonstrated that the local-to-global ratio of GABAA receptor binding potential in the visual cortex predicted the degree of changes in neural activity from EC to EO. This same relationship was also shown in the auditory cortex. Furthermore, the local-to-global ratio of GABAA receptor binding potential in the visual cortex also predicted the change in functional connectivity between the visual and auditory cortex from EC to EO. These findings contribute to our understanding of the role of GABAA receptors in stimulus-induced neural activity in local regions and in inter-regional functional connectivity.

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“…[ 18 F]FMZ was synthesized as published previously (Massaweh et al, 2009). Head movement was minimized with a head-restraining adhesive band.…”

Section: Methodsmentioning

confidence: 99%

GABAA receptors in visual and auditory cortex and neural activity changes during basic visual stimulation

Qin

Duncan

Wiebking

et al. 2012

Front. Hum. Neurosci.

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“…[ 18 F]FMZ was synthesized as published previously (Massaweh et al, 2009 (1 mL+ 40 μL H2O). The residual water was removed by coevaporation to dryness with CH3CN (2× 1 mL) using a stream of nitrogen at 80°C.…”

Section: Radiochemistrymentioning

confidence: 99%

Where in-vivo imaging meets cytoarchitectonics: The relationship between cortical thickness and neuronal density measured with high-resolution [18F]flumazenil-PET

et al. 2011

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“…Apart of structural information, all non-invasive imaging techniques that are used clinically can also provide preclinical information about cerebral blood flow (Zaro-Weber et al 2009) and in some cases penumbral tissue (Massaweh et al 2009; Rivers et al 2006). Being able to detect the molecular or cellular components involved in ischaemic brain damage will also increasingly afford a more targeted intervention (Rojas et al 2007).…”

Section: Serial In Vivo Evaluation Of Stroke Impactmentioning

confidence: 99%

Long-term survival and serial assessment of stroke damage and recovery – practical and methodological considerations.

Modo

2009

Journal of Experimental Stroke and Translational Medicine

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Impairments caused by stroke remain the main cause for adult disability. Despite a vigorous research effort, only 1 thrombolytic treatment has been approved in acute stroke (<3h). The limitations of preclinical studies and how these can be overcome have been the subject of various guidelines. However, often these guidelines focus on the acute stroke setting and omit long-term outcome measures, such as behaviour and neuroimaging. The considerations and practicalities of including the serial assessment of these approaches and their significance to establish therapeutic efficacy are discussed here.

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Improved work-up procedure for the production of [18F]flumazenil and first results of its use with a high-resolution research tomograph in human stroke

Cited by 35 publications

References 22 publications

GABAA receptors in visual and auditory cortex and neural activity changes during basic visual stimulation

GABAA receptors in visual and auditory cortex and neural activity changes during basic visual stimulation

Where in-vivo imaging meets cytoarchitectonics: The relationship between cortical thickness and neuronal density measured with high-resolution [18F]flumazenil-PET

Long-term survival and serial assessment of stroke damage and recovery – practical and methodological considerations.

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