Assessing Glomerular Filtration in Small Animals Using [68Ga]DTPA and [68Ga]EDTA with PET Imaging
Assessing Glomerular Filtration in Small Animals Using [68Ga]DTPA and [68Ga]EDTA with PET Imaging
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DOI：
10.1007/s11307-017-1135-1
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发表时间：
2018-06-01
影响因子：
3.1
通讯作者：
Thews, Oliver
中科院分区：
文献类型：
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作者：
Guendel, Daniel;Pohle, Ulrike;Thews, Oliver
测定肾小球滤过率（GFR）对于临床医学以及临床前动物研究都是必不可少的。使用正电子发射断层扫描（PET）的功能成像允许重复的几乎无创的测量。本研究的目的是开发和评价易于合成的PET示踪剂，用于小动物GFR测量。用Ga-68标记二乙三胺五乙酸（DTPA）和乙二胺四乙酸（EDTA）。在体外测试与血细胞和血浆蛋白的结合。通过PET成像和离体测量分析示踪剂在大鼠中的分布。根据血室（心脏）的时间-活性曲线和肾脏排泄的总示踪剂质量，计算GFR。这些数值直接与相同动物的菊糖清除率进行比较，两种示踪剂都不与血细胞结合。[Ga-68]DPTA而不是[Ga-68]EDTA显示出与血浆蛋白的强结合。因此，[Ga-68]DPTA在血液中停留的时间要长得多，并且在60分钟内只有30%的注射剂量被肾脏消除，而[Ga-68]EDTA的排泄率为89 +/-1%。使用[Ga-68]EDTA计算的GFR与同一动物中测量的菊粉清除率相当。使用[Ga-68]-DPTA，测量值比正常GFR低80%。结果还显示，血室感兴趣体积的定义会影响计算，并可能导致GFR略微高估。[Ga-68]EDTA是小动物PET成像GFR计算的合适示踪剂。该方法易于标记，测定结果与菊粉清除率符合较好。[Ga-68]DTPA由于与血浆蛋白的强结合而导致GFR显著低估，因此不是GFR测量的适当示踪剂。
Determining the glomerular filtration rate (GFR) is essential for clinical medicine but also for pre-clinical animal studies. Functional imaging using positron emission tomography (PET) allows repetitive almost non-invasive measurements. The aim of the study was the development and evaluation of easily synthesizable PET tracers for GFR measurements in small animals.Diethylenetriaminepentaacetic acid (DTPA) and ethylenediaminetetraacetic acid (EDTA) were labeled with Ga-68. The binding to blood cells and plasma proteins was tested in vitro. The distribution of the tracers in rats was analyzed by PET imaging and ex vivo measurements. From the time-activity-curve of the blood compartment (heart) and the total tracer mass excreted by the kidney, the GFR was calculated. These values were compared directly with the inulin clearance in the same animals.Both tracers did not bind to blood cells. [Ga-68]DPTA but not [Ga-68]EDTA showed strong binding to plasma proteins. For this reason, [Ga-68]DPTA stayed much longer in the blood and only 30 % of the injected dose was eliminated by the kidney within 60 min whereas the excretion of [Ga-68]EDTA was 89 +/- 1 %. The calculated GFR using [Ga-68]EDTA was comparable to the measured inulin clearance in the same animal. Using [Ga-68]-DPTA, the measurements led to values which were 80 % below the normal GFR. The results also revealed that definition of the volume of interest for the blood compartment affects the calculation and may lead to a slight overestimation of the GFR.[Ga-68]EDTA is a suitable tracer for GFR calculation from PET imaging in small animals. It is easy to be labeled, and the results are in good accordance with the inulin clearance. [Ga-68]DTPA led to a marked underestimation of GFR due to its strong binding to plasma proteins and is therefore not an appropriate tracer for GFR measurements.