Reference : Single photon emission-computed tomography (SPECT) for functional investigation of th...
Scientific journals : Article
Human health sciences : Radiology, nuclear medicine & imaging
Single photon emission-computed tomography (SPECT) for functional investigation of the proximal tubule in conscious mice.
JOURET, François mailto [Centre Hospitalier Universitaire de Liège - CHU > > Néphrologie >]
Walrand, Stephan [> >]
Parreira, Kleber S. [> >]
Courtoy, Pierre J. [> >]
Pauwels, Stanislas [> >]
Devuyst, Olivier [> >]
Jamar, Francois [> >]
American Journal of Physiology - Renal Physiology
Yes (verified by ORBi)
United States
[en] Animals ; Chloride Channels/deficiency/metabolism ; Cisplatin ; Consciousness ; Kidney/metabolism/radionuclide imaging ; Kidney Cortex/radionuclide imaging ; Kidney Diseases/chemically induced/metabolism ; Kidney Tubules ; Kidney Tubules, Proximal/radionuclide imaging ; Kinetics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Radioisotope Renography ; Radiopharmaceuticals/diagnostic use/pharmacokinetics ; Technetium Tc 99m Dimercaptosuccinic Acid/diagnostic use/pharmacokinetics ; Technetium Tc 99m Mertiatide/diagnostic use ; Tomography, Emission-Computed, Single-Photon ; beta 2-Microglobulin/metabolism
[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.

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