用 99mTc-MAG3 动态闪烁显像评估单侧输尿管梗阻小鼠的肾功能。
Assessment of renal function in mice with unilateral ureteral obstruction using 99mTc-MAG3 dynamic scintigraphy.
机构信息
Radiology and Vanderbilt University Institute of Imaging Science, Nashville, TN, USA.
出版信息
BMC Nephrol. 2012 Dec 10;13:168. doi: 10.1186/1471-2369-13-168.
BACKGROUND
Renal scintigraphy using 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) is widely used for the assessment of renal function in humans. However, the application of this method to animal models of renal disease is currently limited, especially in rodents. Here, we have applied 99mTc-MAG3 renal scintigraphy to a mouse model of unilateral ureteral obstruction (UUO) and evaluated its utility in studying obstructive renal disease.
METHODS
UUO mice were generated by complete ligation of the left ureter. Sham-operated mice were used as a control. Renal function was investigated on days 0, 1, 3, and 6 post-surgery using dynamic planar imaging of 99mTc-MAG3 activity following retro-orbital injection. Time-activity curves (TACs) were produced for individual kidneys and renal function was assessed by 1) the slope of initial 99mTc-MAG3 uptake (SIU), which is related to renal perfusion; 2) peak activity; and 3) the time-to-peak (TTP). The parameters of tubular excretion were not evaluated in this study as 99mTc-MAG3 is not excreted from UUO kidneys.
RESULTS
Compared to sham-operated mice, SIU was remarkably (>60%) reduced in UUO kidneys at day 1 post surgery and the TACs plateaued, indicating that 99mTc-MAG3 is not excreted in these kidneys. The plateau activity in UUO kidneys was relatively low (~40% of sham kidney's peak activity) as early as day1 post surgery, demonstrating that uptake of 99mTc-MAG3 is rapidly reduced in UUO kidneys. The time to plateau in UUO kidneys exceeded 200 sec, suggesting that 99mTc-MAG3 is slowly up-taken in these kidneys. These changes advanced as the disease progressed. SIU, peak activity and TTPs were minimally changed in contra-lateral kidneys during the study period.
CONCLUSIONS
Our data demonstrate that renal uptake of 99mTc-MAG3 is remarkably and rapidly reduced in UUO kidneys, while the changes are minimal in contra-lateral kidneys. The parametric analysis of TACs suggested that renal perfusion as well as tubular uptake is reduced in UUO kidneys. This imaging technique should allow non-invasive assessments of UUO renal injury and enable a more rapid interrogation of novel therapeutic agents and protocols.
背景
使用 99mTc-巯基乙酰三甘氨酸（99mTc-MAG3）进行肾闪烁显像已广泛应用于人类肾功能评估。然而，该方法在肾脏疾病的动物模型中的应用目前受到限制，特别是在啮齿动物中。在这里，我们将 99mTc-MAG3 肾闪烁显像应用于单侧输尿管梗阻（UUO）的小鼠模型，并评估其在研究梗阻性肾病中的应用价值。
方法
通过完全结扎左侧输尿管来生成 UUO 小鼠。假手术组小鼠作为对照。在手术后第 0、1、3 和 6 天，通过眶后注射 99mTc-MAG3 活性的动态平面成像来研究肾功能。为单个肾脏生成时间-活性曲线（TAC），并通过 1）初始 99mTc-MAG3 摄取的斜率（SIU）评估肾功能，该斜率与肾灌注有关；2）峰值活性；3）达峰时间（TTP）。在这项研究中，没有评估管状排泄的参数，因为 99mTc-MAG3 不会从 UUO 肾脏中排泄。
结果
与假手术组相比，UUO 肾脏在手术后第 1 天的 SIU 显著降低（>60%），并且 TAC 呈平台状，表明这些肾脏中未排出 99mTc-MAG3。在手术后第 1 天，UUO 肾脏中的平台活性相对较低（~ sham 肾脏峰值活性的 40%），表明 UUO 肾脏中 99mTc-MAG3 的摄取迅速减少。UUO 肾脏达到平台的时间超过 200 秒，表明这些肾脏中 99mTc-MAG3 的摄取速度较慢。随着疾病的进展，这些变化逐渐加重。在研究期间，对侧肾脏的 SIU、峰值活性和 TTP 变化很小。
结论
我们的数据表明，UUO 肾脏中 99mTc-MAG3 的摄取显著且迅速减少，而对侧肾脏的变化则很小。TAC 的参数分析表明，UUO 肾脏的肾灌注以及管状摄取减少。该成像技术应允许对 UUO 肾脏损伤进行非侵入性评估，并能更快速地研究新型治疗剂和方案。
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