title: Serotonin-to-dopamine transporter ratios in Parkinson disease: Relevance for dyskinesias.
abstract: OBJECTIVE
  To investigate whether a serotonin-to-dopamine terminal ratio is related to the appearance of dyskinesias in patients with Parkinson disease (PD).
  
  
  METHODS
  Twenty-eight patients with idiopathic PD (17 with levodopa-induced dyskinesias [LIDs], 11 without dyskinesias) and 12 age-matched healthy controls were studied with PET and 5[(11)C]-3-amino-4-(2-dimethylaminomethylphenyl-sulfanyl)-benzonitrile ((11)C-DASB) and with SPECT and [(123)I]N-w-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ((123)I-ioflupane), which are in vivo specific markers of the serotonin and dopamine transporters' availability, respectively. We have employed a simplified reference tissue model for the quantification of (11)C-DASB, whereas a semiquantification approach was used for (123)I-ioflupane data. We calculated (11)C-DASB binding to (123)I-ioflupane uptake ratios for the caudate and the putamen.
  
  
  RESULTS
  Patients with PD showed striatal decreases in (11)C-DASB binding potential (p < 0.01) and in (123)I-ioflupane mean uptake (p < 0.001) compared to controls. The mean (11)C-DASB binding to (123)I-ioflupane uptake ratio in the putamen was 0.779 (increased by 75.8% of the controls' mean) for the nondyskinetic group and 0.901 (increased by 103.4% of the controls' mean) for the patients with dyskinesias. There was a statistically significant difference (p < 0.001) in (11)C-DASB binding to (123)I-ioflupane uptake ratio in the putamen between the group of patients with and without dyskinesias. Higher (11)C-DASB to (123)I-ioflupane binding ratios correlated with longer disease duration for the 28 patients with PD (r = 0.52; p < 0.01).
  
  
  CONCLUSIONS
  Serotonin-to-dopamine transporter binding ratio increases as PD progresses and patients experience LIDs. Our findings suggest that, when the dopaminergic innervation in the striatum is critically low, the serotonergic system plays an important role in development of LIDs.
authors.affiliation: From the Neurology Imaging Unit (A.-A.R., P.P.), Centre of Neuroinflammation and Neurodegeneration, Division of Brain Sciences, Hammersmith Campus, Imperial College London; Neurodegeneration Imaging Group (M.P.), Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London; and Radiological Sciences Unit (D.T.), Imperial College Healthcare NHS Trust, London, UK.
authors.forename: Andreas-Antonios
authors.initials: AA
authors.lastname: Roussakis
authors.affiliation: From the Neurology Imaging Unit (A.-A.R., P.P.), Centre of Neuroinflammation and Neurodegeneration, Division of Brain Sciences, Hammersmith Campus, Imperial College London; Neurodegeneration Imaging Group (M.P.), Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London; and Radiological Sciences Unit (D.T.), Imperial College Healthcare NHS Trust, London, UK.
authors.forename: Marios
authors.initials: M
authors.lastname: Politis
authors.affiliation: From the Neurology Imaging Unit (A.-A.R., P.P.), Centre of Neuroinflammation and Neurodegeneration, Division of Brain Sciences, Hammersmith Campus, Imperial College London; Neurodegeneration Imaging Group (M.P.), Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London; and Radiological Sciences Unit (D.T.), Imperial College Healthcare NHS Trust, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Towey
authors.affiliation: From the Neurology Imaging Unit (A.-A.R., P.P.), Centre of Neuroinflammation and Neurodegeneration, Division of Brain Sciences, Hammersmith Campus, Imperial College London; Neurodegeneration Imaging Group (M.P.), Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London; and Radiological Sciences Unit (D.T.), Imperial College Healthcare NHS Trust, London, UK. paola.piccini@imperial.ac.uk.
authors.forename: Paola
authors.initials: P
authors.lastname: Piccini
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D004409:Dyskinesia, Drug-Induced / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007980:Levodopa / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: D015415:Biomarkers; D050483:Dopamine Plasma Membrane Transport Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D007980:Levodopa