Single photon emission-computed tomography (SPECT) for functional investigation of the proximal tubule in conscious mice

1 Division of Nephrology, ; 2 Laboratory of Molecular Imaging and Experimental Radiotherapy, and ; 3 de Duve Institute, CELL Unit, Université catholique de Louvain Medical School, Brussels, Belgium Submitted July 22, 2009 ; accepted in final form November 30, 2009 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-β 2 -microglobulin, which monitors receptor-mediated endocytosis. 99m Tc-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 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-β 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-β 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. receptor-mediated endocytosis; tubular secretion; ClC-5; Dent's disease; radionuclear tracers Address for reprint requests and other correspondence: O. Devuyst, Div. of Nephrology, Université Catholique de Louvain Medical School, Ave. Hippocrate, UCL 54.30, B-1200 Brussels, Belgium (e-mail: olivier.devuyst{at}uclouvain.be ).