1 year ago
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Biomolecules, Vol. 13, Pages 674: Combined In Vivo Microdialysis and PET Studies to Validate [11C]Yohimbine Binding as a Marker of Noradrenaline Release
Biomolecules doi: 10.3390/biom13040674
Authors: Anne Marlene Landau Steen Jakobsen Majken Borup Thomsen Aage Kristian Olsen Alstrup Dariusz Orlowski Jan Jacobsen Gregers Wegener Arne Mørk Jens Christian Hedemann Sørensen Doris J. Doudet
The noradrenaline system attracts attention for its role in mood disorders and neurodegenerative diseases but the lack of well-validated methods impairs our understanding when assessing its function and release in vivo. This study combines simultaneous positron emission tomography (PET) and microdialysis to explore if [11C]yohimbine, a selective antagonist radioligand of the α2 adrenoceptors, may be used to assess in vivo changes in synaptic noradrenaline during acute pharmacological challenges. Anesthetised Göttingen minipigs were positioned in a head holder in a PET/CT device. Microdialysis probes were placed in the thalamus, striatum and cortex and dialysis samples were collected every 10 min. Three 90 min [11C]yohimbine scans were acquired: at baseline and at two timepoints after the administration of amphetamine (1–10 mg/kg), a non-specific releaser of dopamine and noradrenaline, or nisoxetine (1 mg/kg), a specific noradrenaline transporter inhibitor. [11C]yohimbine volumes of distribution (VT) were obtained using the Logan kinetic model. Both challenges induced a significant decrease in yohimbine VT, with time courses reflecting their different mechanisms of action. Dialysis samples revealed a significant increase in noradrenaline extracellular concentrations after challenge and an inverse correlation with changes in yohimbine VT. These data suggest that [11C]yohimbine can be used to evaluate acute variations in synaptic noradrenaline concentrations after pharmacological challenges.
