Ex Vivo and In Vivo Evaluation of the Norepinephrine Transporter Ligand [11C]MRB for Brown Adipose Tissue Imaging

Introduction: 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 [C-11]MRB, a highly selective NET (norepinephrine transporter) ligand for BAT imaging at room temperature, which is not achievable with [F-18]FDG. Methods: PET images of male Sprague-Dawley rats with [F-18]FDG and [C-11]MRB were compared. Relative [F-18]FDG or [C-11]MRB retention at 20, 40 and 60 min post-injection was quantified on awake rats after exposing to cold (4 degrees C for 4 h) or remaining at room temperature. Rats pretreated with unlabeled MRB or nisoxetine 30 min before [C-11]MRB injection were also assessed. The [C-11]MRB metabolite profile in BAT was evaluated. Results: PET imaging demonstrated intense [C-11]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, [F-18]FIDG in BAT was only detected in rats treated with cold. Ex vivo results were concordant with the imaging findings; i.e. the uptake of [C-11]MRB in BAT was 3 times higher than that of [F-18]FDG at room temperature (P = 0.009), and the significant cold-stimulated uptake in BAT with [F-18]FDG (10-fold, P = 0.001) was not observed with [C-11]MRB (P = 0.082). HPLC analysis revealed 94%-99% of total radioactivity in BAT represented unchanged [C-11]MRB. Conclusions: Our study demonstrates that BAT could be specifically labeled with [C-11]MRB at room temperature and under cold conditions, supporting a NET-PET strategy for imaging BAT in humans under basal conditions. (c) 2012 Elsevier Inc. All rights reserved.