In vivo imaging of neuromelanin in Parkinson's disease using 18F-AV-1451 PET.
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
The tau tangle ligand (18)F-AV-1451 ((18)F-T807) binds to neuromelanin in the midbrain, and may therefore be a measure of the pigmented dopaminergic neuronal count in the substantia nigra. Parkinson's disease is characterized by progressive loss of dopaminergic neurons. Extrapolation of post-mortem data predicts that a ∼30% decline of nigral dopamine neurons is necessary to cause motor symptoms in Parkinson's disease. Putamen dopamine terminal loss at disease onset most likely exceeds that of the nigral cell bodies and has been estimated to be of the order of 50-70%. We investigated the utility of (18)F-AV-1451 positron emission tomography to visualize the concentration of nigral neuromelanin in Parkinson's disease and correlated the findings to dopamine transporter density, measured by (123)I-FP-CIT single photon emission computed tomography. A total of 17 patients with idiopathic Parkinson's disease and 16 age- and sex-matched control subjects had (18)F-AV-1451 positron emission tomography using a Siemens high-resolution research tomograph. Twelve patients with Parkinson's disease also received a standardized (123)I-FP-CIT single photon emission computed tomography scan at our imaging facility. Many of the patients with Parkinson's disease displayed visually apparent decreased (18)F-AV-1451 signal in the midbrain. On quantitation, patients showed a 30% mean decrease in total nigral (18)F-AV-1451 volume of distribution compared with controls (P = 0.004), but there was an overlap of the individual ranges. We saw no significant correlation between symptom dominant side and contralateral nigral volume of distribution. There was no correlation between nigral (18)F-AV-1451 volume of distribution and age or time since diagnosis. In the subset of 12 patients, who also had a (123)I-FP-CIT scan, the mean total striatal dopamine transporter signal was decreased by 45% and the mean total (18)F-AV-1451 substantia nigra volume of distribution was decreased by 33% after median disease duration of 4.7 years (0.5-12.4 years). (18)F-AV-1451 positron emission tomography may be the first radiotracer to reflect the loss of pigmented neurons in the substantia nigra of parkinsonian patients. The magnitude of the nigral signal loss was smaller than the decrease in striatal dopamine transporter signal measured by dopamine transporter single photon emission computed tomography. These findings suggest a more severe loss of striatal nerve terminal function compared with neuronal cell bodies, in accordance with the post-mortem literature.
Date Issued
2016-05-05
Date Acceptance
2016-03-14
Citation
Brain, 2016, 139 (7), pp.2039-2049
ISSN
1460-2156
Publisher
Oxford University Press
Start Page
2039
End Page
2049
Journal / Book Title
Brain
Volume
139
Issue
7
Copyright Statement
This is a pre-copyedited, author-produced PDF of an article accepted for publication in Brain following peer review. The version of record In vivo imaging of neuromelanin in Parkinson’s disease using 18F-AV-1451 PET
Allan K. Hansen, Karoline Knudsen, Thea P. Lillethorup, Anne M. Landau, Peter Parbo, Tatyana Fedorova, Hélène Audrain, Dirk Bender, Karen Østergaard, David J. Brooks, Per Borghammer
Brain Jul 2016, 139 (7) 2039-2049; is available online at: https://dx.doi.org/10.1093/brain/aww098
Allan K. Hansen, Karoline Knudsen, Thea P. Lillethorup, Anne M. Landau, Peter Parbo, Tatyana Fedorova, Hélène Audrain, Dirk Bender, Karen Østergaard, David J. Brooks, Per Borghammer
Brain Jul 2016, 139 (7) 2039-2049; is available online at: https://dx.doi.org/10.1093/brain/aww098
Subjects
Science & Technology
Life Sciences & Biomedicine
Clinical Neurology
Neurosciences
Neurosciences & Neurology
AV-1451
PET
neuromelanin
Parkinson
dopamine transporter
POSITRON-EMISSION-TOMOGRAPHY
SUBSTANTIA-NIGRA
HUMAN-BRAIN
LEWY BODY
TYROSINE-HYDROXYLASE
NEURONAL LOSS
RATING-SCALE
EARLY-STAGE
SPECT
DEGENERATION
Neurology & Neurosurgery
11 Medical And Health Sciences
17 Psychology And Cognitive Sciences
Publication Status
Published