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

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 [(18)F]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 [(18)F]MK-9470 uptake were present in the brain of pentobarbital and isoflurane rats as compared to control conditions. Relative [(18)F]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 [(18)F]MK-9470.