Noradrenergic deficits in Parkinson's disease imaged with (11)C-MeNER

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Rationale: Degeneration of noradrenergic neurons may underlie the disabling non-motor symptoms in patients with Parkinson's disease. 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 (11)C-MeNER is a highly selective antagonist of noradrenaline transporters, and positron emission tomography (PET) suggests that it is suitable for quantitative neuroimaging of noradrenergic deficits in human brain in vivo. In the present investigation, we used PET with (11)C-MeNER to map the density of noradrenaline transporters in groups of patients with Parkinsonńs disease and age-matched healthy controls. Methods: Following administration of (11)C-MeNER, 15 non-demented patients with Parkinsonńs disease and 10 healthy subjects underwent 90-minute dynamic PET. We determined the binding potential of (11)C-MeNER relative to non-displaceable binding by multilinear analysis (MA1) and the simplified reference tissue model 2 (SRTM2). Results: The binding potentials of (11)C-MeNER were reduced in the Parkinsonńs disease group, compared to the control subjects, with regionally significant declines in the thalamus, hypothalamus, and nucleus ruber. Tremor was significantly associated with preserved tracer binding. Conclusion: This is first specific quantification of noradrenergic denervation in Parkinsonńs disease patients in vivo. In agreement with predictions from determinations in vitro, we discovered a decline of noradrenergic projections in vivo in brain of Parkinsonńs disease patients.

Original languageEnglish
JournalJournal of Nuclear Medicine
Volume59
Issue4
Pages (from-to)659-664
Number of pages6
ISSN0161-5505
DOIs
Publication statusPublished - 2018

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  • Journal Article

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