PET Center, Department of Diagnostic Radiology, Yale University, New Haven, CT 06520, USA.
Nucl Med Biol. 2012 Oct;39(7):1081-6. doi: 10.1016/j.nucmedbio.2012.04.005. Epub 2012 May 16.
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.
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.
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.
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.
有人提出，人类的棕色脂肪组织（BAT）可能在能量平衡和肥胖中发挥作用。我们使用室温下高度选择性的去甲肾上腺素转运体（NET）配体 [(11)C]MRB 进行了离体和在体评估，而这在使用 [(18)F]FDG 时是无法实现的。
比较了雄性 Sprague-Dawley 大鼠的 [(18)F]FDG 和 [(11)C]MRB 的 PET 图像。在将大鼠暴露于冷环境（4°C 4 小时）或保持在室温下后，在清醒大鼠上定量测量注射后 20、40 和 60 分钟时相对 [(18)F]FDG 或 [(11)C]MRB 的保留率。还评估了在注射 [(11)C]MRB 前 30 分钟用未标记的 MRB 或奈索西汀预处理的大鼠。评估了 BAT 中 [(11)C]MRB 代谢产物的特征。
PET 成像显示，在室温下和冷暴露的大鼠的肩胛间 BAT 中均可见强烈的 [(11)C]MRB 摄取（SUV 为 2.9 至 3.3），而用未标记的 MRB 预处理则明显减少了这种摄取；相反，在接受冷处理的大鼠中仅检测到 BAT 中的 [(18)F]FDG。离体结果与成像结果一致；即，BAT 中 [(11)C]MRB 的摄取量是室温下 [(18)F]FDG 的 3 倍（P=0.009），而在冷刺激下，[(18)F]FDG 在 BAT 中的摄取量显著增加（10 倍，P=0.001），而 [(11)C]MRB 则没有观察到（P=0.082）。HPLC 分析显示 BAT 中 94%-99%的总放射性代表未改变的 [(11)C]MRB。
我们的研究表明，BAT 可以在室温下和冷条件下特异性标记 [(11)C]MRB，支持在基础条件下对人类 BAT 进行 NET-PET 成像的策略。
