Division of Nephrology, Université catholique de Louvain Medical School, Brussels, Belgium.
Am J Physiol Renal Physiol. 2010 Feb;298(2):F454-60. doi: 10.1152/ajprenal.00413.2009. Epub 2009 Dec 2.
Noninvasive analysis of renal function in conscious mice is necessary to optimize the use of mouse models. In this study, we evaluated whether single photon emission-computed tomography (SPECT) using specific radionuclear tracers can be used to analyze changes in renal proximal tubule functions. The tracers included (99m)TC- dimercaptosuccinic acid ((99m)Tc-DMSA), which is used for cortex imaging; (99m)Tc-mercaptoacetyltriglycine ((99m)Tc-MAG3), used for dynamic renography; and (123)I-beta(2)-microglobulin, which monitors receptor-mediated endocytosis. (99m)Tc-DMSA SPECT imaging was shown to delineate the functional renal cortex with a approximately 1-mm spatial resolution and accumulated in the cortex reaching a plateau 5 h after injection. The cortical uptake of (99m)Tc-DMSA was abolished in Clcn5 knockout mice, a model of proximal tubule dysfunction. Dynamic renography with (99m)Tc-MAG3 in conscious mice demonstrated rapid extraction from blood, renal accumulation, and subsequent tubular secretion. Anesthesia induced a significant delay in the (99m)Tc-MAG3 clearance. The tubular reabsorption of (123)I-beta(2)-microglobulin was strongly impaired in the Clcn5 knockout mice, with defective tubular processing and loss of the native tracer in urine, reflecting proximal tubule dysfunction. Longitudinal studies in a model of cisplatin-induced acute tubular injury revealed a correlation between tubular recovery and (123)I-beta(2)-microglobulin uptake. These data show that SPECT imaging with well-validated radiotracers allows in vivo investigations of specific proximal tubule functions in conscious mice.
在清醒小鼠中进行非侵入性肾功能分析对于优化小鼠模型的使用是必要的。在这项研究中，我们评估了使用特定放射性核素示踪剂的单光子发射计算机断层扫描（SPECT）是否可用于分析肾近端小管功能的变化。示踪剂包括用于皮质成像的（99m）Tc-二巯丁二酸（（99m）Tc-DMSA）；用于动态肾图的（99m）Tc-巯基乙酰三甘氨酸（（99m）Tc-MAG3）；以及监测受体介导的内吞作用的（123）I-β2-微球蛋白。（99m）Tc-DMSA SPECT 成像显示可在约 1 毫米的空间分辨率下描绘功能正常的肾皮质，并且在注射后 5 小时达到皮质累积的平台期。在 Clcn5 敲除小鼠（近端小管功能障碍的模型）中，（99m）Tc-DMSA 的皮质摄取被消除。在清醒小鼠中进行的（99m）Tc-MAG3 动态肾图研究表明，该示踪剂从血液中快速提取，在肾脏中积聚，随后进行肾小管分泌。麻醉会导致（99m）Tc-MAG3 清除的显著延迟。Clcn5 敲除小鼠中（123）I-β2-微球蛋白的管状重吸收严重受损，肾小管处理有缺陷，尿液中丢失天然示踪剂，反映出近端小管功能障碍。顺铂诱导的急性肾小管损伤模型中的纵向研究显示，肾小管恢复与（123）I-β2-微球蛋白摄取之间存在相关性。这些数据表明，使用经过充分验证的放射性示踪剂的 SPECT 成像可在清醒小鼠中进行特定的近端小管功能的体内研究。
