Noradrenergic Deficits in Parkinson Disease Imaged with 11C-MeNER

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

doi:10.2967/jnumed.117.190975

Noradrenergic Deficits in Parkinson Disease Imaged with ¹¹C-MeNER

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

Department of Neuroscience

21 Citations (Scopus)

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-(a-(2-methoxyphenoxy)benzyl)mor-pholine (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 non-demented 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_ND¹¹C-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 language	English
Journal	Journal of Nuclear Medicine
Volume	59
Issue number	4
Pages (from-to)	659-664
Number of pages	6
ISSN	0161-5505
DOIs	https://doi.org/10.2967/jnumed.117.190975
Publication status	Published - 1 Apr 2018

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@article{858f72b11b8d48ed81def7290e74f0bc,

title = "Noradrenergic Deficits in Parkinson Disease Imaged with 11C-MeNER",

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-(a-(2-methoxyphenoxy)benzyl)mor-pholine (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 non-demented patients with PD and 10 healthy subjects underwent 90-min dynamic PET. We determined 11C-MeNER binding potential relative to nondisplaceable binding potential (BPND) 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 BPND11C-MeNER BPND 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.",

author = "Adjmal Nahimi and Michael Sommerauer and Kinnerup, {Martin B} and Karen {\O}stergaard and Michael Winterdahl and Jan Jacobsen and Anna Schacht and Birger Johnsen and Damholdt, {Malene F.} and Per Borghammer and Albert Gjedde",

note = "{\textcopyright} 2018 by the Society of Nuclear Medicine and Molecular Imaging.",

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doi = "10.2967/jnumed.117.190975",

language = "English",

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T1 - Noradrenergic Deficits in Parkinson Disease Imaged with 11C-MeNER

AU - Nahimi, Adjmal

AU - Sommerauer, Michael

AU - Kinnerup, Martin B

AU - Østergaard, Karen

AU - Winterdahl, Michael

AU - Jacobsen, Jan

AU - Schacht, Anna

AU - Johnsen, Birger

AU - Damholdt, Malene F.

AU - Borghammer, Per

AU - Gjedde, Albert

PY - 2018/4/1

Y1 - 2018/4/1

N2 - 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-(a-(2-methoxyphenoxy)benzyl)mor-pholine (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 non-demented patients with PD and 10 healthy subjects underwent 90-min dynamic PET. We determined 11C-MeNER binding potential relative to nondisplaceable binding potential (BPND) 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 BPND11C-MeNER BPND 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.

AB - 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-(a-(2-methoxyphenoxy)benzyl)mor-pholine (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 non-demented patients with PD and 10 healthy subjects underwent 90-min dynamic PET. We determined 11C-MeNER binding potential relative to nondisplaceable binding potential (BPND) 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 BPND11C-MeNER BPND 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.

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DO - 10.2967/jnumed.117.190975

M3 - Journal article

C2 - 28848039

SN - 0161-5505

VL - 59

SP - 659

EP - 664

JO - The Journal of Nuclear Medicine

JF - The Journal of Nuclear Medicine

IS - 4

ER -