title: Ex vivo and in vivo evaluation of the norepinephrine transporter ligand [11C]MRB for brown adipose tissue imaging.
abstract: BACKGROUND
  It has been suggested that brown adipose tissue (BAT) in humans may play a role in energy balance and obesity. We conducted ex vivo and in vivo evaluation using [(11)C]MRB, a highly selective NET (norepinephrine transporter) ligand for BAT imaging at room temperature, which is not achievable with [(18)F]FDG.
  
  
  METHODS
  PET images of male Sprague-Dawley rats with [(18)F]FDG and [(11)C]MRB were compared. Relative [(18)F]FDG or [(11)C]MRB retention at 20, 40 and 60 min post-injection was quantified on awake rats after exposing to cold (4°C for 4h) or remaining at room temperature. Rats pretreated with unlabeled MRB or nisoxetine 30 min before [(11)C]MRB injection were also assessed. The [(11)C]MRB metabolite profile in BAT was evaluated.
  
  
  RESULTS
  PET imaging demonstrated intense [(11)C]MRB uptake (SUV of 2.9 to 3.3) in the interscapular BAT of both room temperature and cold-exposed rats and this uptake was significantly diminished by pretreatment with unlabeled MRB; in contrast, [(18)F]FDG in BAT was only detected in rats treated with cold. Ex vivo results were concordant with the imaging findings; i.e. the uptake of [(11)C]MRB in BAT was 3 times higher than that of [(18)F]FDG at room temperature (P=0.009), and the significant cold-stimulated uptake in BAT with [(18)F]FDG (10-fold, P=0.001) was not observed with [(11)C]MRB (P=0.082). HPLC analysis revealed 94%-99% of total radioactivity in BAT represented unchanged [(11)C]MRB.
  
  
  CONCLUSIONS
  Our study demonstrates that BAT could be specifically labeled with [(11)C]MRB at room temperature and under cold conditions, supporting a NET-PET strategy for imaging BAT in humans under basal conditions.
authors.affiliation: PET Center, Department of Diagnostic Radiology, Yale University, New Haven, CT 06520, USA.
authors.forename: Shu-fei
authors.initials: SF
authors.lastname: Lin
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Fan
authors.forename: Catherine Weikart
authors.initials: CW
authors.lastname: Yeckel
authors.forename: David
authors.initials: D
authors.lastname: Weinzimmer
authors.forename: Tim
authors.initials: T
authors.lastname: Mulnix
authors.forename: Jean-Dominique
authors.initials: JD
authors.lastname: Gallezot
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sherwin
authors.forename: Yu-Shin
authors.initials: YS
authors.lastname: Ding
mesh_terms: D002001:Adipose Tissue, Brown / Q000000981:diagnostic imaging* / Q000378:metabolism; D000818:Animals; D005473:Fluoxetine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D008024:Ligands; D008297:Male; D009025:Morpholines / Q000378:metabolism* / Q000493:pharmacokinetics; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077593:Reboxetine; D014851:Wakefulness
chemical_list: D008024:Ligands; D009025:Morpholines; D050484:Norepinephrine Plasma Membrane Transport Proteins; C524178:O-methyl reboxetine; D005473:Fluoxetine; C011386:nisoxetine; D000077593:Reboxetine