Gastrointestinal transit measurements in mice with 99mTc-DTPA-labeled activated charcoal using NanoSPECT-CT.
Gastrointestinal transit measurements in mice with 99mTc-DTPA-labeled activated charcoal using NanoSPECT-CT.
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DOI：
10.1186/2191-219x-3-60
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发表时间：
2013-08-02
期刊：
影响因子：
3.2
通讯作者：
Golay X
中科院分区：
文献类型：
--
作者：
Padmanabhan P;Grosse J;Asad AB;Radda GK;Golay X
胃肠道(GI)障碍通常与糖尿病、肥胖症和高血压等慢性疾病有关。直接的后果是便秘或腹泻，这是肠易激综合征的相反方面，更间接的是，食欲改变、饱腹感、腹胀、腹胀，最终导致营养吸收改变。此外，胃肠道滞留和通过时间被认为是决定口服药物释放部位和生物利用度的重要因素。为了便于了解相关的生理和病理过程，有必要在动物模型中监测肠道运动。在这里，我们描述了一种用单光子发射计算机断层扫描(SPECT)检测的~(99m)Tc-CH-DTPA标记的活性炭二乙三胺五乙酸(99mTC-CH-DTPA)研究胃肠道通过时间的方法。将TC-DTPA吸附在活性碳上，经口服给受台盼蓝污染的129SvEv小鼠(n=4，50~80MBq/只，n=11)。分别于1、3、6、12、22h用SPECT-CT测量胃肠道放射性分布和运动情况。此外，为了验证胃肠道瞬时时间的成像，应用洛哌丁胺(0.25 mg/只，n=3)延迟胃肠道通过时间。99mTC-CH-DTPA灌胃后6~7h为直肠放射性峰值。1h后，丸剂进入小肠，进入盲肠和结肠。6h和8h时，盲肠、升结肠、横结肠、降结肠以及直肠均有明显标记。几粒小球被储存在直肠内以供排便。22小时后，胃中几乎没有活动，横结肠或其他胃肠道部位也没有检测到活动。相反，给药6h后，仅盲肠和部分横结肠被标记。22h后，两种结构都保留了大量的标记。这一延迟已被非放射性标记染料台盼蓝GI测量所证实(n=4)。在这里，我们提出了第一个对小鼠胃肠道通过时间的非侵入性研究，允许明确区分赋形剂和氯哌丁胺治疗的动物。该技术可用于小鼠胃肠动力的研究。
Gastrointestinal (GI) disorders are commonly associated with chronic conditions such as diabetes, obesity, and hypertension. Direct consequences are obstipation or diarrhea as opposite aspects of the irritable bowel syndrome, and more indirectly, alteration of appetite, feeling of fullness, flatulence, bloatedness, and eventually leading to altered absorption of nutrients. Moreover, GI retention and passage times have been recognized as important factors in determining the release site and hence the bioavailability of orally administered drugs. To facilitate the understanding of physiological and pathological processes involved, it is necessary to monitor the gut motility in animal models. Here, we describe a method for studying the GI transit time using technetium-labeled activated charcoal diethylenetriaminepentaacetic acid (99mTc-Ch-DTPA) detected by single-photon emission computed tomography (SPECT). Tc-DTPA was adsorbed onto activated charcoal and administered orally to trypan blue-tainted (n = 4) 129SvEv mice (50 to 80 MBq/animal, n = 11). The exact distribution and movement of radioactivity in the gastrointestinal tract was measured at intervals of 1, 3, 6, 12, and 22 h by SPECT-CT. In addition, in order to validate the imaging of GI transient time, loperamide (0.25 mg/animal, n = 3) was used to delay the GI transit. The transit time measured as the peak radioactivity occurring in the rectum was 6 to 7 h after gavaging of 99mTc-Ch-DTPA. After 1 h, the bolus had passed into the small intestine and entered the cecum and the colon. At 6 and 8 h, the cecum, the ascending, transverse, and descending colon, and the rectum showed significant labeling. Several pellets were stored in the rectum for defecation. After 22 h, little activity remained in the stomach and none was detected in the transverse colon or other GI locations. In contrast, 6 h after administration of loperamide, only the cecum and part of the transverse colon were labeled. After 22 h, both structures retained significant amount of label. This delay has been verified by non-radiolabeled dye trypan blue GI measurements (n = 4). Here, we present the first non-invasive study of mouse GI transit time, allowing clear differentiation between vehicle- and loperamide-treated animals. This technique is useful for the investigation of GI motility in mice.