title: In vivo imaging of neuromelanin in Parkinson's disease using 18F-AV-1451 PET.
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.
authors.affiliation: 1 Department of Nuclear Medicine and PET-Centre, Aarhus University Hospital, Denmark.
authors.forename: Allan K
authors.initials: AK
authors.lastname: Hansen
authors.affiliation: 1 Department of Nuclear Medicine and PET-Centre, Aarhus University Hospital, Denmark.
authors.forename: Karoline
authors.initials: K
authors.lastname: Knudsen
authors.affiliation: 1 Department of Nuclear Medicine and PET-Centre, Aarhus University Hospital, Denmark.
authors.forename: Thea P
authors.initials: TP
authors.lastname: Lillethorup
authors.affiliation: 1 Department of Nuclear Medicine and PET-Centre, Aarhus University Hospital, Denmark 2 Translational Neuropsychiatry Unit, Institute of Clinical Medicine, Aarhus University, Denmark.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Landau
authors.affiliation: 1 Department of Nuclear Medicine and PET-Centre, Aarhus University Hospital, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Parbo
authors.affiliation: 1 Department of Nuclear Medicine and PET-Centre, Aarhus University Hospital, Denmark.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Fedorova
authors.affiliation: 1 Department of Nuclear Medicine and PET-Centre, Aarhus University Hospital, Denmark.
authors.forename: Hélène
authors.initials: H
authors.lastname: Audrain
authors.affiliation: 1 Department of Nuclear Medicine and PET-Centre, Aarhus University Hospital, Denmark.
authors.forename: Dirk
authors.initials: D
authors.lastname: Bender
authors.affiliation: 3 Department of Neurology, Institute of Clinical Medicine, Aarhus University, Denmark.
authors.forename: Karen
authors.initials: K
authors.lastname: Østergaard
authors.affiliation: 1 Department of Nuclear Medicine and PET-Centre, Aarhus University Hospital, Denmark 4 Division of Neuroscience, Department of Medicine, Imperial College London, UK 5 Division of Neuroscience, Newcastle University, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Brooks
authors.affiliation: 1 Department of Nuclear Medicine and PET-Centre, Aarhus University Hospital, Denmark perborgh@rm.dk.
authors.forename: Per
authors.initials: P
authors.lastname: Borghammer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000378:metabolism; D005260:Female; D005462:Fluorine Radioisotopes / Q000378:metabolism*; D006801:Humans; D008297:Male; D008543:Melanins / Q000378:metabolism*; D008875:Middle Aged; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D013378:Substantia Nigra / Q000000981:diagnostic imaging / Q000378:metabolism*; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014326:Tropanes / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D050483:Dopamine Plasma Membrane Transport Proteins; D005462:Fluorine Radioisotopes; D008543:Melanins; D014326:Tropanes; C014121:neuromelanin; C087552:2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane
keywords: AV-1451; PET; Parkinson; dopamine transporter; neuromelanin