Sensitivity of [C]ORM-13070 to increased extracellular noradrenaline in the CNS - a PET study in human subjects.
Rationale: No validated methods have been available for studying brain noradrenergic neurotransmission in vivo in humans. Positron emission tomography (PET) radiotracers are widely used in clinical drug development targeted to brain receptors and can also in some cases be employed to monitor extrace...
| Publicado en: | Psychopharmacology Vol. 232; no. 21/22; pp. 4169 - 4179 |
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| Autores principales: | , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Nov2015
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=110261427&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 110261427 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00333158 EJD jtl: Psychopharmacology issn: 00333158 maglogo: N pubinfo: dt: Nov2015 vid: 232 iid: 21/22 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 110261427 10.1007/s00213-015-3941-y 110261427 ppf: 4169 ppct: 10 formats: fmt: @attributes: type: P tig: atl: Sensitivity of [C]ORM-13070 to increased extracellular noradrenaline in the CNS - a PET study in human subjects. aug: au: Lehto, Jussi Johansson, Jarkko Vuorilehto, Lauri Luoto, Pauliina Arponen, Eveliina Scheinin, Harry Rouru, Juha Scheinin, Mika affil: Turku PET Centre, University of Turku and Turku University Hospital, Turku Finland sug: ab: Rationale: No validated methods have been available for studying brain noradrenergic neurotransmission in vivo in humans. Positron emission tomography (PET) radiotracers are widely used in clinical drug development targeted to brain receptors and can also in some cases be employed to monitor extracellular (synaptic) neurotransmitter concentrations. Objectives: The objective of this study is to test the sensitivity of [C]ORM-13070 uptake to increased concentrations of extracellular (synaptic) noradrenaline in the human brain. Methods: Eight subjects underwent a control PET scan with [C]ORM-13070, a subtype-selective α-adrenoceptor antagonist radioligand, and two PET scans after two different noradrenaline challenges, i.e. during ketamine infusion and after a dose 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 and 5-30 min post injection and quantified with the ratio method. Voxel-based analysis was performed with average bound per free (B/F) ratio images. Results: Both noradrenaline challenges were consistently associated with 10-20 % ( p < 0.05) reductions in tracer uptake in the dorsal striatum, as determined with region-of-interest-based analysis. Voxel-based analysis revealed significant reductions in B/F ratios in the dorsal striatum, in the brain stem and in several cortical areas. Reductions of 24 and 23 % were detected in the peak putamen clusters with ketamine and atomoxetine + cold, respectively. Conclusion: Direct experimental support was gained for the suitability of [C]ORM-13070 for imaging of brain noradrenergic neurotransmission. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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