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 99mTC- dimercaptosuccinic acid (99mTc-DMSA), which is used for cortex imaging; 99mTc-mercaptoacetyltriglycine (99mTc-MAG3), used for dynamic renography; and 123I-β2-microglobulin, which monitors receptor-mediated endocytosis. 99mTc-DMSA SPECT imaging was shown to delineate the functional renal cortex with a ∼1-mm spatial resolution and accumulated in the cortex reaching a plateau 5 h after injection. The cortical uptake of 99mTc-DMSA was abolished in Clcn5 knockout mice, a model of proximal tubule dysfunction. Dynamic renography with 99mTc-MAG3 in conscious mice demonstrated rapid extraction from blood, renal accumulation, and subsequent tubular secretion. Anesthesia induced a significant delay in the 99mTc-MAG3 clearance. The tubular reabsorption of 123I-β2-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 123I-β2-microglobulin uptake. These data show that SPECT imaging with well-validated radiotracers allows in vivo investigations of specific proximal tubule functions in conscious mice.
Differentiation of Malignant Glioma and Metastatic Brain Tumor by Thallium-201 Single Photon Emission Computed Tomography