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

• Published in: American journal of physiology. Renal physiology 2010-02, Vol.298 (2), p.F454-F460
• Main Authors: Jouret, François, Walrand, Stéphan, Parreira, Kleber S, Courtoy, Pierre J, Pauwels, Stanislas, Devuyst, Olivier, Jamar, François
• Format: Article
• Language: English
• Subjects: Anesthesia; Animals; beta 2-Microglobulin - metabolism; Chloride Channels - deficiency; Chloride Channels - metabolism; Cisplatin; Consciousness; Kidney - diagnostic imaging; Kidney - metabolism; Kidney Cortex - diagnostic imaging; Kidney Diseases - chemically induced; Kidney Diseases - metabolism; Kidney Tubules; Kidney Tubules, Proximal - diagnostic imaging; Kidneys; Kinetics; Mice; Mice, Inbred C57BL; Mice, Knockout; Radioisotope Renography; Radiopharmaceuticals - pharmacokinetics; Rodents; Studies; Technetium Tc 99m Dimercaptosuccinic Acid - pharmacokinetics; Technetium Tc 99m Mertiatide; Tomography; Tomography, Emission-Computed, Single-Photon
• ISSN: 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.00413.2009

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-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.