[en] 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.
Disciplines :
Radiology, nuclear medicine & imaging
Author, co-author :
JOURET, François ; Centre Hospitalier Universitaire de Liège - CHU > Néphrologie
Walrand, Stephan
Parreira, Kleber S.
Courtoy, Pierre J.
Pauwels, Stanislas
Devuyst, Olivier
Jamar, Francois
Language :
English
Title :
Single photon emission-computed tomography (SPECT) for functional investigation of the proximal tubule in conscious mice.
Publication date :
2010
Journal title :
American Journal of Physiology. Renal, Fluid and Electrolyte Physiology
ISSN :
0363-6127
eISSN :
2161-1157
Publisher :
American Physiological Society, United States - Maryland
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