Detecting a dexmedetomidine‐evoked reduction of noradrenaline release in the human brain with the alpha2C‐adrenoceptor PET ligand [11C]ORM‐13070

PET imaging can for some neurotransmitters be used to measure synaptic neurotransmitter concentrations. The objective of this study was to test whether the receptor binding of the α_2C‐AR antagonist PET tracer [¹¹C]ORM‐13070 would increase in response to reductions in synaptic noradrenaline, evoked by dexmedetomidine as a sympatholytic drug challenge. Six subjects underwent a control PET scan and two dexmedetomidine PET scans. Dexmedetomidine was infused with target plasma concentrations of 0.6 and 0.2 ng/ml. Tracer binding was measured by voxel‐based analysis of bound per free (B/F) images. ROI‐based analysis was performed in the dorsal striatum and in the thalamus. Vital signs and drug concentrations in plasma were measured and the sedative effect was estimated with the visual analog scale. In the voxel‐based analysis, dexmedetomidine administration was associated with a tendency to increased B/F tracer in the right thalamus (mean, +17%, P = 0.14, and +19%, P = 0.05, with the low and high dose, respectively). Tracer binding in the dorsal striatum was unaffected by dexmedetomidine. A cluster with significantly increased B/F tracer (+42%, P = 0.01) was seen in the right superior temporal gyrus with low‐dose dexmedetomidine, but not after the high dose. Brain uptake of [¹¹C]ORM‐13070 has previously been shown to be reduced in conditions of increased synaptic noradrenaline concentrations. In this study, tracer binding in the thalamus tended to increase in accordance with reduced activity of noradrenergic projections from the locus coeruleus, but statistical significance was not reached. Synapse 70:57–65, 2016. © 2015 Wiley Periodicals, Inc.