Noradrenergic deficits in Parkinson disease imaged with 11C-MeNER

Adjmal Nahimi*, Michael Sommerauer, Martin B. Kinnerup, Karen Østergaard, Michael Wintherdahl, Jan Jacobsen, Anna Schacht, Birger Johnsen, Malene F. Damholdt, Per Borghammer, Albert Gjedde

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Degeneration of noradrenergic neurons may underlie the disabling nonmotor symptoms in patients with Parkinson disease (PD). Quantification of the loss of noradrenergic neurons by means of neuroimaging has been limited by the lack of radioligands that are selective for noradrenergic neurotransmission. The radioligand ( S,S)- 11C-2-(α-(2-methoxyphenoxy)benzyl)morpholine ( 11C-MeNER) is a highly selective inhibitor of noradrenaline transporters, and PET studies suggest that this radioligand is suitable for quantitative neuroimaging of noradrenergic deficits in human brain in vivo. In the present investigation, we used PET with 11C-MeNER to map the density of noradrenaline transporters in groups of patients with PD and age-matched healthy controls. Methods: After administration of 11C-MeNER, 15 nondemented patients with PD and 10 healthy subjects underwent 90-min dynamic PET. We determined 11C-MeNER binding potential relative to nondisplaceable binding potential (BP ND) by multilinear analysis, simplified reference tissue model 2, and multilinear reference tissue model 2. Results: Metabolism of 11C-MeNER did not differ between groups. The simplified reference tissue model 2 and the multilinear reference tissue model 2 were used to determine 11C-MeNER BP ND 11C-MeNER BP ND was reduced in the PD group compared with the control subjects, with regionally significant declines in the thalamus and nucleus ruber. Tremor was associated with higher tracer binding in the PD group on multivariate regression analysis. Conclusion: To our knowledge, this was the first specific quantification of noradrenergic denervation in PD patients in vivo. In agreement with predictions from determinations in vitro, we discovered a decline of noradrenergic projections in vivo in brain of PD patients.

Original languageEnglish
JournalJournal of Nuclear Medicine
Volume59
Issue number4
Pages (from-to)659-664
ISSN0161-5505
DOIs
Publication statusPublished - Apr 2018

Keywords

  • 11C-MeNER
  • Noradrenaline transporter
  • Parkinson disease
  • Positron emission tomography
  • Parkinson Disease/diagnostic imaging
  • Norepinephrine Plasma Membrane Transport Proteins/metabolism
  • Humans
  • Middle Aged
  • Male
  • Positron-Emission Tomography
  • Morpholines
  • Case-Control Studies
  • Image Processing, Computer-Assisted
  • Female

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