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

IntroductionIt 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 [11C]MRB, a highly selective NET (norepinephrine transporter) ligand for BAT imaging at room temperature, which is not achievable with [18F]FDG.MethodsPET images of male Sprague–Dawley rats with [18F]FDG and [11C]MRB were compared. Relative [18F]FDG or [11C]MRB retention at 20, 40 and 60 min post-injection was quantified on awake rats after exposing to cold (4 °C for 4 h) or remaining at room temperature. Rats pretreated with unlabeled MRB or nisoxetine 30 min before [11C]MRB injection were also assessed. The [11C]MRB metabolite profile in BAT was evaluated.ResultsPET imaging demonstrated intense [11C]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, [18F]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 [11C]MRB in BAT was 3 times higher than that of [18F]FDG at room temperature (P = 0.009), and the significant cold-stimulated uptake in BAT with [18F]FDG (10-fold, P = 0.001) was not observed with [11C]MRB (P = 0.082). HPLC analysis revealed 94%–99% of total radioactivity in BAT represented unchanged [11C]MRB.ConclusionsOur study demonstrates that BAT could be specifically labeled with [11C]MRB at room temperature and under cold conditions, supporting a NET-PET strategy for imaging BAT in humans under basal conditions.