Baba Shingo, Engles James M, Huso David L, Ishimori Takayoshi, Wahl Richard L
Division of Nuclear Medicine, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
J Nucl Med. 2007 Oct;48(10):1715-23. doi: 10.2967/jnumed.107.041715. Epub 2007 Sep 14.
Our objective was to determine whether multiple clinically useful radiotracers accumulate in brown adipose tissue (BAT) and to assess their uptake in rats kept at room temperature or exposed to a cold environment.
The following radiotracers were injected intravenously into groups of 6 female Wistar rats: (201)Tl-chloride (TlCl), (123)I-metaiodobenzylguanidine (MIBG), (99m)Tc-sestamibi (MIBI), (18)F- or (3)H-FDG, (3)H-l-methionine, and (3)H-thymidine. BAT-stimulated animals were maintained at 4 degrees C for 4 h before tracer injection, whereas control animals were kept at approximately 22.5 degrees C. The animals were sacrificed at 20-60 min after tracer injection, and BAT, major organs, and blood were extracted, weighed, and measured for radioactivity. The localization of uncoupling protein-1, glucose transporter-1, and norepinephrine transporter was evaluated with immunohistochemical staining in both groups.
We determined the percentage injected dose (%ID) per gram of each radiotracer in interscapular BAT, normalized to blood %ID/g. In control animals, this uptake ratio (+/-SD) was 8.44 +/- 3.39 for (201)TlCl, 9.77 +/- 6.06 for (123)I-MIBG, 37.30 +/- 14.42 for (99m)Tc-MIBI, 5.47 +/- 4.44 for (18)F- or (3)H-FDG, 1.93 +/- 0.87 for (3)H-l-methionine, and 1.22 +/- 0.74 for (3)H-thymidine. Compared with uptake at room temperature, uptake after exposure to cold increased 26.4-fold (P < 0.01) for (18)F- or (3)H-FDG and increased significantly (P < 0.05) for (201)Tl (2.04-fold), (123)I-MIBG (3.25-fold), and (3)H-l-methionine (3.11-fold). Immunohistochemical staining revealed increased glucose transporter-1 and norepinephrine transporter expression in BAT cell membranes and blood vessels after exposure to cold, whereas uncoupling protein-1 was expressed in the cytoplasm under both control and cold-stimulated conditions.
BAT uptake of (18)F- or (3)H-FDG, (123)I-MIBG, and (3)H-l-methionine was significantly increased over the control state by exposure to cold. Increased uptake of (201)TlCl relative to blood in cold-stimulated BAT suggests that blood flow in BAT is increased by exposure to cold. The greater increased uptake with (18)F- or (3)H-FDG, (123)I-MIBG, and (3)H-l-methionine, and the immunohistostaining findings, suggest that other factors in addition to blood flow (e.g., increased metabolism, increased transport, or metabolic trapping of the tracers) are involved in cold-stimulated BAT activation. Knowledge that high uptake in BAT may possibly be observed on clinical scans using several radiotracers, especially after patients are exposed to the cold, may lead to more accurate interpretation of clinical studies.
我们的目的是确定多种具有临床应用价值的放射性示踪剂是否会在棕色脂肪组织（BAT）中蓄积，并评估它们在处于室温或暴露于寒冷环境的大鼠体内的摄取情况。
将以下放射性示踪剂静脉注射到每组6只雌性Wistar大鼠体内：氯化铊（201）Tl（TlCl）、间碘苄胍（123）I（MIBG）、锝（99m）Tc-甲氧基异丁基异腈（MIBI）、氟（18）F或氢（3）H标记的氟代脱氧葡萄糖（FDG）、氢（3）H标记的L-蛋氨酸以及氢（3）H标记的胸腺嘧啶核苷。在注射示踪剂前，将受BAT刺激的动物置于4℃环境中4小时，而对照动物则保持在约22.5℃。在注射示踪剂后20 - 60分钟处死动物，取出BAT、主要器官及血液，称重并测量放射性。通过免疫组织化学染色评估两组动物中解偶联蛋白-1、葡萄糖转运蛋白-1和去甲肾上腺素转运蛋白的定位。
我们测定了肩胛间BAT中每克各放射性示踪剂的注射剂量百分比（%ID），并以血液中的%ID/g进行标准化。在对照动物中，该摄取率（±标准差）对于（201）TlCl为8.44±3.39，对于（123）I-MIBG为9.77±6.06，对于（99m）Tc-MIBI为37.30±14.42，对于（18）F或（3）H-FDG为5.47±4.44，对于（3）H-L-蛋氨酸为1.93±0.87，对于（3）H-胸腺嘧啶核苷为1.22±0.74。与室温下的摄取相比，暴露于寒冷环境后，（18）F或（3）H-FDG的摄取增加了26.4倍（P < 0.01），（201）Tl增加了2.04倍（P < 0.05），（123）I-MIBG增加了3.25倍（P < 0.05），（3）H-L-蛋氨酸增加了3.11倍（P < 0.05）。免疫组织化学染色显示，暴露于寒冷环境后，BAT细胞膜和血管中的葡萄糖转运蛋白-1和去甲肾上腺素转运蛋白表达增加，而在对照和寒冷刺激条件下，解偶联蛋白-1均在细胞质中表达。
暴露于寒冷环境使BAT对（18）F或（3）H-FDG、（123）I-MIBG和（3）H-L-蛋氨酸的摄取相对于对照状态显著增加。寒冷刺激的BAT中（201）TlCl相对于血液的摄取增加表明，暴露于寒冷环境会使BAT中的血流量增加。（18）F或（3）H-FDG、（123）I-MIBG和（3）H-L-蛋氨酸摄取的更大增加以及免疫组织化学染色结果表明，除血流量外的其他因素（例如，代谢增加、转运增加或示踪剂的代谢捕获）参与了寒冷刺激的BAT激活。了解在使用几种放射性示踪剂进行临床扫描时，尤其是在患者暴露于寒冷环境后，可能会在BAT中观察到高摄取，这可能会导致对临床研究的更准确解读。
