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 [(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.
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 [(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.
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