Bracco Imaging SpA, Bracco Research Centre, Colleretto Giacosa, TO, Italy.
Bracco Suisse SA, Plan-les-Ouates, GE, Switzerland.
J Magn Reson Imaging. 2018 Mar;47(3):746-752. doi: 10.1002/jmri.25822. Epub 2017 Jul 21.
To compare the levels of gadolinium in the blood, cerebrum, cerebellum, liver, femur, kidneys, and skin after multiple exposure of rats to the macrocyclic gadolinium-based contrast agents (GBCAs) gadoterate, gadobutrol, and gadoteridol.
Fifty male Wistar Han rats were randomized to three exposure groups (n = 15 per group) and one control group (n = 5). Animals in the exposure groups received a total of 20 GBCA administrations (four administrations per week for 5 consecutive weeks) at a dose of 0.6 mmol/kg bodyweight. After a 28-day recovery period animals were sacrificed and the blood and tissues harvested for determination of gadolinium (Gd) levels. Gd determination was performed by inductively coupled plasma mass spectrometry (ICP-MS).
After 28 days' recovery no Gd was found in the blood, liver, or skin of any animal in any group. Significantly lower levels of Gd were noted with gadoteridol compared to gadoterate and gadobutrol in the cerebellum (0.150 ± 0.022 vs. 0.292 ± 0.057 and 0.287 ± 0.056 nmol/g, respectively; P < 0.001), cerebrum (0.116 ± 0.036 vs. 0.250 ± 0.032 and 0.263 ± 0.045 nmol/g, respectively; P < 0.001), and kidneys (25 ± 13 vs. 139 ± 88 [P < 0.01] and 204 ± 109 [P < 0.001], respectively). Higher levels of Gd were noted in the femur (7.48 ± 1.37 vs. 5.69 ± 1.75 and 8.60 ± 2.04 nmol/g, respectively) with significantly less Gd determined for gadoterate than for gadobutrol (P < 0.001) and gadoteridol (P < 0.05).
Differences exist between macrocyclic agents in terms of their propensity to accumulate in tissues. The observed differences in Gd concentration point to differences in GBCA washout rates in this setting and in this experimental model, with gadoteridol being the GBCA that is most efficiently removed from both cerebral and renal tissues.
2 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018;47:746-752.
比较多次暴露于大环钆基对比剂（GBCA）后大鼠血液、大脑、小脑、肝脏、股骨、肾脏和皮肤中的钆水平。
将 50 只雄性 Wistar Han 大鼠随机分为三组（每组 15 只）和一组对照组（n = 5）。暴露组的动物共接受 20 次 GBCA 给药（每周 4 次，连续 5 周），剂量为 0.6 mmol/kg 体重。28 天恢复期后，处死动物并采集血液和组织以测定钆（Gd）水平。使用电感耦合等离子体质谱法（ICP-MS）进行 Gd 测定。
在任何一组的任何动物的血液、肝脏或皮肤中，在 28 天恢复期后均未发现 Gd。与 gadoterate 和 gadobutrol 相比，gadoteridol 在小脑（0.150 ± 0.022 比 0.292 ± 0.057 和 0.287 ± 0.056 nmol/g；P < 0.001）、大脑（0.116 ± 0.036 比 0.250 ± 0.032 和 0.263 ± 0.045 nmol/g；P < 0.001）和肾脏（25 ± 13 比 139 ± 88 [P < 0.01] 和 204 ± 109 [P < 0.001]）中，Gd 水平显著较低。股骨中的 Gd 水平较高（7.48 ± 1.37 比 5.69 ± 1.75 和 8.60 ± 2.04 nmol/g），与 gadobutrol（P < 0.001）和 gadoteridol（P < 0.05）相比，Gd 水平明显较低。
大环试剂在其在组织中积累的倾向方面存在差异。在这种情况下，在这个实验模型中，观察到的 Gd 浓度差异表明 GBCA 的清除率存在差异，gadoteridol 是从大脑和肾脏组织中最有效地清除的 GBCA。
2 技术功效：第 5 阶段 J. Magn. Reson. Imaging 2018;47:746-752.
