Department of Anesthesiology, University of Colorado-Denver School of Medicine, 1775 N Aurora Ct, M20-3103, Aurora, CO 80045, USA.
Radiology. 2010 May;255(2):517-26. doi: 10.1148/radiol.09091134. Epub 2010 Mar 23.
To determine the feasibility of T2-weighted magnetic resonance (MR) imaging in the noninvasive quantification of renal inflammation by using superparamagnetic iron oxide (SPIO) nanoparticles targeted to tissue-bound C3 activation fragments in a mouse model of lupus nephritis.
All animal procedures were approved by the University of Colorado-Denver animal care and use committee. SPIO nanoparticles were encapsulated by using amine-functionalized phospholipids. A recombinant protein containing the C3d-binding region of complement receptor type 2 (CR2) was then conjugated to the surface of the SPIO nanoparticle. Five MRL/lpr mice (a model of lupus nephritis) and six C57BL/6 wild-type mice were assessed with T2-weighted MR imaging at baseline and after SPIO injection. The same five MRL/lpr mice and three C57BL/6 mice also underwent MR imaging after injection of CR2-targeted SPIO. A series of T2-weighted pulses with 16 echo times was used to enable precise T2 mapping and calculation of T2 relaxation times in the cortex and outer and inner medulla of the kidneys, as well as in the spleen, muscle, and fat. The effects of treatment and animal genotype on T2 relaxation times were analyzed with repeated-measures analysis of variance.
At baseline, the T2-weighted signal intensity in the kidneys of MRL/lpr mice was higher than that in the kidneys of wild-type mice. Injection of untargeted SPIO did not alter the T2-weighted signal in the kidneys in either strain of mice. Injection of CR2-targeted SPIO in MRL/lpr mice, however, caused a significant accumulation of targeted iron oxide with a subsequent decrease in T2 relaxation times in the cortex and outer and inner medulla of the kidneys. No changes in T2 relaxation time were observed in the wild-type mice after injection of targeted SPIO.
Injection of CR2-conjugated SPIO caused a significant reduction in T2-weighted MR imaging signal and T2 relaxation time in nephritic kidneys.
通过使用针对组织结合的 C3 激活片段的超顺磁氧化铁 (SPIO) 纳米粒子，在狼疮肾炎小鼠模型中，确定 T2 加权磁共振 (MR) 成像在非侵入性量化肾炎症中的可行性。
所有动物程序均获得科罗拉多大学丹佛分校动物护理和使用委员会的批准。SPIO 纳米粒子被胺官能化磷脂包封。然后，将包含补体受体 2 (CR2) 的 C3d 结合区的重组蛋白与 SPIO 纳米粒子的表面缀合。对 5 只 MRL/lpr 小鼠（狼疮肾炎模型）和 6 只 C57BL/6 野生型小鼠进行 T2 加权 MR 成像，在基线和 SPIO 注射后进行评估。同样的 5 只 MRL/lpr 小鼠和 3 只 C57BL/6 小鼠也在注射 CR2 靶向 SPIO 后进行了 MR 成像。使用具有 16 个回波时间的一系列 T2 加权脉冲，以实现精确的 T2 映射和计算肾脏皮质、外髓和内髓以及脾脏、肌肉和脂肪的 T2 弛豫时间。使用重复测量方差分析分析治疗和动物基因型对 T2 弛豫时间的影响。
在基线时，MRL/lpr 小鼠肾脏的 T2 加权信号强度高于野生型小鼠肾脏的信号强度。注射未靶向的 SPIO 不会改变两种小鼠肾脏的 T2 加权信号。然而，在 MRL/lpr 小鼠中注射 CR2 靶向 SPIO 会导致靶向氧化铁的显著积累，随后导致肾脏皮质、外髓和内髓的 T2 弛豫时间降低。在注射靶向 SPIO 后，野生型小鼠的 T2 弛豫时间没有变化。
注射 CR2 缀合的 SPIO 导致肾炎肾脏的 T2 加权 MR 成像信号和 T2 弛豫时间显著降低。
