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The effect of anaesthesia on [18F]MK-9470 binding to the type 1 cannabinoid receptor in the rat brain

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Abstract

Purpose

Small animal PET can be applied to study molecular processes in animal models of a variety of human diseases. In order to keep the animals in a restricted position during imaging, anaesthesia is in many instances inevitable. Using small animal PET and ex vivo autoradiography, we examined the influence of pentobarbital and isoflurane anaesthesia on the rat brain uptake of [18F]MK-9470, a radioligand for the type 1 cannabinoid receptor.

Methods

PET imaging was performed on adult Wistar rats under pentobarbital (n = 6) and isoflurane anaesthesia (n = 7), and under control conditions (free moving during tracer uptake, n = 8). Parametric PET images were generated, anatomically standardized and analysed by voxel-based Statistical Parametric Mapping and a predefined volume of interest approach. Immediately after in vivo PET, brains were processed for ex vivo autoradiography using manually placed regions of interest. An extra group (n = 6) was included ex vivo, in which animals were intravenously injected without the use of anaesthetics.

Results

Using in vivo and ex vivo molecular imaging techniques, no significant changes in absolute [18F]MK-9470 uptake were present in the brain of pentobarbital and isoflurane rats as compared to control conditions. Relative [18F]MK-9470 uptake PET values obtained applying global scaling were, however, decreased in the cortex under both anaesthetics (pentobarbital: −13.3±1.4%; isoflurane −8.7 ± 3.1%), while an increase was seen in the cerebellum by 13.5 ± 4.0% and 13.9 ± 4.1% under pentobarbital and isoflurane, respectively. Ex vivo results were in agreement with in vivo findings.

Conclusion

These findings suggest a similar, regionally specific interference of pentobarbital and isoflurane anaesthesia with in vivo CB1 receptor imaging using [18F]MK-9470.

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Acknowledgements

The authors thank the Leuven PET radiopharmacy team for [18F]MK-9470 production and Merck & Co., Inc. for their availability of the [18F]MK-9470 precursor. Financial support of the Research Council of the Katholieke Universiteit Leuven (OT/05/58), the Fund for Scientific Research, Flanders, Belgium (FWO/G.0548.06) and the Institute for the Promotion of Innovation by Science and Technology in Flanders (SBO50151) is gratefully acknowledged. This work is also supported by MoSAIC, the K.U. Leuven Molecular Small Animal Imaging Center (KUL EF/05/08). KVL is a Senior Clinical Investigator of the Flemish Fund of Scientific Research. Part of this work is performed under the European Commission FP6 project Diagnostic Molecular Imaging (DIMI), LSHB-CT-2005-512146.

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Correspondence to Cindy Casteels.

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Casteels, C., Bormans, G. & Van Laere, K. The effect of anaesthesia on [18F]MK-9470 binding to the type 1 cannabinoid receptor in the rat brain. Eur J Nucl Med Mol Imaging 37, 1164–1173 (2010). https://doi.org/10.1007/s00259-010-1383-7

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  • DOI: https://doi.org/10.1007/s00259-010-1383-7

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