Quantitative assessment of brown adipose tissue metabolic activity and volume using 18F-FDG PET/CT and β3-adrenergic receptor activation.
Quantitative assessment of brown adipose tissue metabolic activity and volume using 18F-FDG PET/CT and β3-adrenergic receptor activation.
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DOI：
10.1186/2191-219x-1-30
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发表时间：
2011-12-01
期刊：
影响因子：
3.2
通讯作者：
Mukherjee J
中科院分区：
文献类型：
--
作者：
Mirbolooki MR;Constantinescu CC;Pan ML;Mukherjee J
体内棕色脂肪组织 [BAT] 代谢对于开发对抗肥胖和糖尿病的新策略至关重要。目前，BAT 在低温下激活，并使用 2-脱氧-2-18F-氟-D-葡萄糖 [18F-FDG] 正电子发射断层扫描 [PET] 进行测量。我们报告了在环境温度下使用 (R, R)-5-[2-[2,3-(3-氯苯基)-2-羟乙基-氨基]丙基]-1,3-苯并间二氧杂环戊烯-2,2-二羧酸二钠盐[CL316,243]（选择性 β3-肾上腺素受体激动剂）并通过 18F-FDG PET/计算机断层扫描 [CT] 进行测量。对照和 CL316,243 治疗（2 mg/kg）的雄性 Sprague-Dawley 大鼠被给予 18F-FDG 进行 PET/CT 研究，并与低温下的动物进行比较。使用普萘洛尔（5 mg/kg）进行受体阻断实验。通过在 18F-FDG 给药前 30 分钟注射 0.1 至 1 mg/kg 来研究 CL316,243 的剂量效应。通过放射自显影证实成像结果，并进行组织学证实 BAT 激活。 CL316,243 激活的肩胛间 BAT [IBAT]、颈部、主动脉周围和肋间 BAT 通过 PET 清晰可见。与对照相比，CL316,243 使 IBAT 的 18F-FDG 摄取增加了 12 倍，而冷暴露则增加了 1.1 倍。使用普萘洛尔腹膜内给药，CL 激活的 IBAT 的 18F-FDG 摄取减少了 96.0%。剂量为 0.1、0.5 和 1 mg/kg CL 时，IBAT 的平均 18F-FDG 摄取量分别增加了 3.6、3.5 和 7.6 倍。离体 18F-FDG 放射自显影和 IBAT 横切面的组织学证实 CL 激活组中的强烈摄取，并且通过 PET 可视化激活的 IBAT。我们的研究表明，在环境温度下，可以在啮齿动物模型中使用 CL316,243 通过 18F-FDG PET 评估 BAT 代谢活性。这为研究BAT代谢提供了可行可靠的方法。
Brown adipose tissue [BAT] metabolism in vivo is vital for the development of novel strategies in combating obesity and diabetes. Currently, BAT is activated at low temperatures and measured using 2-deoxy-2-18F-fluoro-D-glucose [18F-FDG] positron-emission tomography [PET]. We report the use of β3-adrenergic receptor-mediated activation of BAT at ambient temperatures using (R, R)-5-[2-[2,3-(3-chlorphenyl)-2-hydroxyethyl-amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate, disodium salt [CL316,243] (a selective β3-adrenoceptor agonist) and measured by 18F-FDG PET/computed tomography [CT]. Control and CL316,243-treated (2 mg/kg) male Sprague-Dawley rats were administered with 18F-FDG for PET/CT studies and were compared to animals at cold temperatures. Receptor-blocking experiments were carried out using propranolol (5 mg/kg). Dose effects of CL316,243 were studied by injecting 0.1 to 1 mg/kg 30 min prior to 18F-FDG administration. Imaging results were confirmed by autoradiography, and histology was done to confirm BAT activation. CL316,243-activated interscapular BAT [IBAT], cervical, periaortic, and intercostal BATs were clearly visualized by PET. 18F-FDG uptake of IBAT was increased 12-fold by CL316,243 vs. 1.1-fold by cold exposure when compared to controls. 18F-FDG uptake of the CL-activated IBAT was reduced by 96.0% using intraperitoneal administration of propranolol. Average 18F-FDG uptake of IBAT increased 3.6-, 3.5-, and 7.6-fold by doses of 0.1, 0.5, and 1 mg/kg CL, respectively. Ex vivo 18F-FDG autoradiography and histology of transverse sections of IBAT confirmed intense uptake in the CL-activated group and activated IBAT visualized by PET. Our study indicated that BAT metabolic activity could be evaluated by 18F-FDG PET using CL316,243 at ambient temperature in the rodent model. This provides a feasible and reliable method to study BAT metabolism.