title: [¹⁸F]FDOPA uptake in the raphe nuclei complex reflects serotonin transporter availability. A combined [¹⁸F]FDOPA and [¹¹C]DASB PET study in Parkinson's disease.
abstract: Brain uptake of [(18)F]FDOPA, measured with PET, reflects the activity of aromatic amino acid decarboxylase, an enzyme largely expressed in monoaminergic nerve terminals. This enzyme catalyzes a number of decarboxylation reactions including conversion of l-dopa into dopamine and 5-hydroxytryptophan into serotonin. For more than 20years [(18)F]FDOPA PET has been used to assess dopaminergic nigrostriatal dysfunction in patients with Parkinson's disease (PD). More recently, however, [(18)F]FDOPA PET has also been employed as a marker of serotoninergic and noradrenergic function in PD patients. In this study, we provide further evidence in support of the view that [(18)F]FDOPA PET can be used to evaluate the distribution and the function of serotoninergic systems in the brain. Eighteen patients with PD were investigated with both [(18)F]FDOPA and [(11)C]DASB PET, the latter being a marker of serotonin transport (SERT) availability. We then assessed the relationship between measurements of the two tracers within brain serotoninergic structures. [(18)F]FDOPA uptake in the median raphe nuclei complex of PD patients was significantly correlated with SERT availability in the same structure. Trends towards significant correlations between [(18)F]FDOPA Ki values and [(11)C]DASB binding values were also observed in the hypothalamus and the anterior cingulate cortex, suggesting a serotoninergic contribution to [(18)F]FDOPA uptake in these regions. Conversely, no correlations were found in brain structures with mixed dopaminergic, serotoninergic and noradrenergic innervations, or with predominant dopaminergic innervation. These findings provide evidence that [(18)F]FDOPA PET represents a valid marker of raphe serotoninergic function in PD and supports previous studies where [(18)F]FDOPA PET has been used to assess serotoninergic function in PD.
authors.affiliation: Centre for Neuroscience, Department of Medicine, Imperial College, London, UK. nicola.pavese@imperial.ac.uk
authors.forename: N
authors.initials: N
authors.lastname: Pavese
authors.forename: B S
authors.initials: BS
authors.lastname: Simpson
authors.forename: V
authors.initials: V
authors.lastname: Metta
authors.forename: A
authors.initials: A
authors.lastname: Ramlackhansingh
authors.forename: K Ray
authors.initials: KR
authors.lastname: Chaudhuri
authors.forename: D J
authors.initials: DJ
authors.lastname: Brooks
mesh_terms: D000368:Aged; D000814:Aniline Compounds / Q000493:pharmacokinetics*; D001682:Biological Availability; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008297:Male; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011903:Raphe Nuclei / Q000000981:diagnostic imaging / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013440:Sulfides / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: C412822:3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile; D000814:Aniline Compounds; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins; D013440:Sulfides; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine