Department of Nuclear Medicine, University Hospital, Halle (Saale), Germany.
Institute of Physiology, University Halle, Halle (Saale), Germany.
Mol Imaging Biol. 2018 Jun;20(3):457-464. doi: 10.1007/s11307-017-1135-1.
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]DPTA but not [Ga]EDTA showed strong binding to plasma proteins. For this reason, [Ga]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]EDTA was 89 ± 1 %. The calculated GFR using [Ga]EDTA was comparable to the measured inulin clearance in the same animal. Using [Ga]-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]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]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.
测定肾小球滤过率（GFR）对于临床医学和临床前动物研究都至关重要。正电子发射断层扫描（PET）的功能成像可以进行重复的、几乎非侵入性的测量。本研究的目的是开发和评估易于合成的 PET 示踪剂，用于小动物的 GFR 测量。
二乙烯三胺五乙酸（DTPA）和乙二胺四乙酸（EDTA）与 Ga-68 标记。在体外测试它们与血细胞和血浆蛋白的结合情况。通过 PET 成像和离体测量分析示踪剂在大鼠体内的分布。根据血液池（心脏）的时间-活性曲线和肾脏排出的总示踪剂质量，计算 GFR。这些值与同一动物的菊粉清除率直接比较。
两种示踪剂均不与血细胞结合。[Ga]DPTA 而不是[Ga]EDTA 与血浆蛋白有很强的结合。因此，[Ga]DPTA 在血液中停留的时间更长，在 60 分钟内只有 30%的注射剂量通过肾脏排出，而[Ga]EDTA 的排出率为 89%±1%。使用[Ga]EDTA 计算的 GFR 与同一动物测量的菊粉清除率相当。使用[Ga]-DPTA，测量结果导致值比正常 GFR 低 80%。结果还表明，定义血液池的感兴趣容积会影响计算，并可能导致 GFR 的轻微高估。
[Ga]EDTA 是小动物 PET 成像中计算 GFR 的合适示踪剂。它易于标记，结果与菊粉清除率吻合良好。[Ga]DTPA 由于与血浆蛋白的强结合而导致 GFR 明显低估，因此不是测量 GFR 的合适示踪剂。
