title: Quantitative analysis of norepinephrine transporter in the human brain using PET with (S,S)-18F-FMeNER-D2.
abstract: (S,S)-18F-FMeNER-D2 was recently developed as a radioligand for the measurement of norepinephrine transporter imaging with PET. In this study, a norepinephrine transporter was visualized in the human brain using this radioligand with PET and quantified by several methods.
  
  
  METHODS
  PET scans were performed on 10 healthy men after intravenous injection of (S,S)-18F-FMeNER-D2. Binding potential relative to nondisplaceable binding (BP(ND)) was quantified by the indirect kinetic, simplified reference-tissue model (SRTM), multilinear reference-tissue model (MRTM), and ratio methods. The indirect kinetic method was used as the gold standard and was compared with the SRTM method with scan times of 240 and 180 min, the MRTM method with a scan time of 240 min, and the ratio method with a time integration interval of 120-180 min. The caudate was used as reference brain region.
  
  
  RESULTS
  Regional radioactivity was highest in the thalamus and lowest in the caudate during PET scanning. BP(ND) values by the indirect kinetic method were 0.54 +/- 0.19 and 0.35 +/- 0.25 in the thalamus and locus coeruleus, respectively. BP(ND) values found by the SRTM, MRTM, and ratio methods agreed with the values demonstrated by the indirect kinetic method (r = 0.81-0.92).
  
  
  CONCLUSIONS
  The regional distribution of (S,S)-18F-FMeNER-D2 in our study agreed with that demonstrated by previous PET and postmortem studies of norepinephrine transporter in the human brain. The ratio method with a time integration interval of 120-180 min will be useful for clinical research of psychiatric disorders for estimation of norepinephrine transporter occupancy by antidepressants without requiring arterial blood sampling and dynamic PET.
authors.affiliation: Molecular Neuroimaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Arakawa
authors.forename: Masaki
authors.initials: M
authors.lastname: Okumura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
authors.forename: Chie
authors.initials: C
authors.lastname: Seki
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Takahashi
authors.forename: Harumasa
authors.initials: H
authors.lastname: Takano
authors.forename: Ryuji
authors.initials: R
authors.lastname: Nakao
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Suzuki
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Okubo
authors.forename: Christer
authors.initials: C
authors.lastname: Halldin
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Suhara
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D005462:Fluorine Radioisotopes; D006801:Humans; D008024:Ligands; D008297:Male; D009025:Morpholines / Q000737:chemistry / Q000493:pharmacokinetics*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics*; D013237:Stereoisomerism; D013788:Thalamus / Q000000981:diagnostic imaging / Q000378:metabolism
chemical_list: C506462:2-(alpha-(2-fluoromethoxyphenoxy)benzyl)morpholine; D005462:Fluorine Radioisotopes; D008024:Ligands; D009025:Morpholines; D050484:Norepinephrine Plasma Membrane Transport Proteins; D019275:Radiopharmaceuticals