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In vivo imaging of neuromelanin in Parkinson’s disease using 18 F-AV-1451 PET

2016; Oxford University Press; Volume: 139; Issue: 7 Linguagem: Inglês

10.1093/brain/aww098

1460-2156

Allan K. Hansen, Karoline Knudsen, Thea P. Lillethorup, Anne M. Landau, Peter Parbo, Tatyana D. Fedorova, Hélène Audrain, Dirk Bender, Karen Østergaard, David J. Brooks, Per Borghammer,

Neurological disorders and treatments

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. The progression rate of dopaminergic cell loss in Parkinson’s disease remains uncertain. Using [ 18 F]AV-1451 PET, Hansen et al. demonstrate a decreased midbrain neuromelanin signal in patients in vivo that may reflect the loss of nigral dopamine neurons. [ 18 F]AV-1451 PET could serve as a biomarker in trials of putative neuroprotective agents.