Volume 4 Supplement 1

European Society for Neurochemistry Biannual Conference: Molecular Mechanisms of Regulation in the Nervous System

Open Access

Imaging of α2C-adrenoceptors in the living brain: a method to monitor noradrenaline release?

  • Mika Scheinin1,
  • Jussi Lehto1,
  • Jarkko Johansson2,
  • Pauliina Luoto2,
  • Eveliina Arponen2,
  • Lauri Vuorilehto1,
  • Harry Scheinin1 and
  • Juha Rouru3
SpringerPlus20154(Suppl 1):L20

https://doi.org/10.1186/2193-1801-4-S1-L20

Published: 12 June 2015

Keywords

Adrenoceptornoradrenalinepositron emission tomography

Objectives

The PET tracer [11C]ORM-13070 was recently validated for receptor occupancy analysis of brain α2C-adrenoceptors, and PET experiments in monkeys and humans indicated that tracer uptake into the caudate and putamen was reduced by interventions that increased synaptic noradrenaline concentrations in the brain [13]. This study aimed to confirm the sensitivity of [11C]ORM-13070 binding to increased levels of synaptic noradrenaline.

Methods

PET imaging of the brain was performed with a 3D High Resolution Research Tomograph. Eight subjects underwent a control [11C]ORM-13070 PET scan and two PET scans after two different noradrenaline challenges, i.e. a sub-anaesthetic infusion of ketamine and oral intake of atomoxetine combined with cold stimulation. Tracer uptake in the caudate nucleus and putamen was described with AUC values in scan time windows of 10-20 min and 5-30 min post injection, and quantified with the ratio method. Voxel-based analysis was performed with average B/F images. Both challenges caused small but statistically significant (10-20%, p<0.05) reductions in tracer uptake in both target regions. Voxel-based analysis revealed significant clusters in the dorsal putamen with both challenges. Ketamine was associated with significant elevations in circulating noradrenaline and adrenaline levels, while the atomoxetine + cold treatment was not. Strong experimental support was gained for the feasibility of [11C]ORM-13070 PET imaging of brain noradrenergic neurotransmission.

Authors’ Affiliations

(1)
University of Turku
(2)
Turku PET Centre, TYKS
(3)
Orion Corporation

References

  1. Lehto J, et al.: . Eur J Nucl Med Mol Imaging 2015, 42: 120-7. 10.1007/s00259-014-2899-zView ArticleGoogle Scholar
  2. Lehto J, et al.: . Synapse 2015, 69: 172-81. 10.1002/syn.21798View ArticleGoogle Scholar
  3. Finnema SJ, et al.: . Int J Neuropsychopharmacol. 2015; in pressGoogle Scholar

Copyright

© Scheinin et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.