title: [11C]NS8880, a promising PET radiotracer targeting the norepinephrine transporter.
abstract: BACKGROUND
  Positron emission tomography (PET) imaging of the norepinephrine transporter (NET) is still hindered by the availability of useful PET imaging probes. The present study describes the radiosynthesis and pre-clinical evaluation of a new compound, exo-3-(6-methoxypyridin-2-yloxy)-8-H-8-azabicyclo[3.2.1]octane (NS8880), targeting NET. NS8880 has an in vitro binding profile comparable to desipramine and is structurally not related to reboxetine.
  
  
  METHODS
  Labeling of NS8880 with [(11)C] was achieved by a non-conventional technique: substitution of pyridinyl fluorine with [(11)C]methanolate in a Boc-protected precursor. The isolated [(11)C]NS8880 was evaluated pre-clinically both in a pig model (PET scanning) and in a rat model (μPET scanning) and compared to (S,S)-[(11)C]-O-methylreboxetine ([(11)C]MeNER).
  
  
  RESULTS
  The radiolabeling technique yielded [(11)C]NS8880 in low (<10%) but still useful yields with high purity. The PET in vivo evaluation in pig and rat revealed a rapid brain uptake of [(11)C]NS8880 and fast obtaining of equilibrium. Highest binding was observed in thalamic and hypothalamic regions. Pretreatment with desipramine efficiently reduced binding of [(11)C]NS8880.
  
  
  CONCLUSIONS
  Based on the pre-clinical results obtained so far [(11)C]NS8880 displays promising properties for PET imaging of NET.
authors.affiliation: PET Center, Aarhus University Hospital, DK-8000 Aarhus C, Denmark. Electronic address: karina@pet.auh.dk.
authors.forename: Karina H
authors.initials: KH
authors.lastname: Vase
authors.affiliation: DanPET AB, Rosenstigen 7, SE-216 19 Malmö, Sweden.
authors.forename: Dan
authors.initials: D
authors.lastname: Peters
authors.affiliation: NeuroSearch A/S, Pederstrupsvej 93, DK-2750 Ballerup, Denmark.
authors.forename: Elsebet Ø
authors.initials: EØ
authors.lastname: Nielsen
authors.affiliation: PET Center, Aarhus University Hospital, DK-8000 Aarhus C, Denmark.
authors.forename: Aage K O
authors.initials: AK
authors.lastname: Alstrup
authors.affiliation: PET Center, Aarhus University Hospital, DK-8000 Aarhus C, Denmark.
authors.forename: Dirk
authors.initials: D
authors.lastname: Bender
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D005260:Female; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D057054:Molecular Imaging / Q000379:methods*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism*; D009795:Octanes / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D009928:Organ Specificity; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013552:Swine; D014018:Tissue Distribution
chemical_list: D002250:Carbon Radioisotopes; D050484:Norepinephrine Plasma Membrane Transport Proteins; D009795:Octanes; D019275:Radiopharmaceuticals
keywords: MeNER; NS8880; Norepinephrine transporter; PET; Preclinical evaluation; Radiosynthesis