title: Single photon emission-computed tomography (SPECT) for functional investigation of the proximal tubule in conscious mice.
abstract: 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.
authors: Division of Nephrology, Université catholique de Louvain Medical School, Brussels, Belgium.
authors: François
authors: F
authors: Jouret
authors: Stéphan
authors: S
authors: Walrand
authors: Kleber S
authors: KS
authors: Parreira
authors: Pierre J
authors: PJ
authors: Courtoy
authors: Stanislas
authors: S
authors: Pauwels
authors: Olivier
authors: O
authors: Devuyst
authors: François
authors: F
authors: Jamar
mesh_terms: D000818:Animals; D018118:Chloride Channels / Q000172:deficiency / Q000378:metabolism; D002945:Cisplatin; D003243:Consciousness; D007668:Kidney / Q000000981:diagnostic imaging / Q000378:metabolism; D007672:Kidney Cortex / Q000000981:diagnostic imaging; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism; D007684:Kidney Tubules; D007687:Kidney Tubules, Proximal / Q000000981:diagnostic imaging*; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011866:Radioisotope Renography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D019783:Technetium Tc 99m Dimercaptosuccinic Acid / Q000493:pharmacokinetics; D017263:Technetium Tc 99m Mertiatide; D015899:Tomography, Emission-Computed, Single-Photon; D001613:beta 2-Microglobulin / Q000378:metabolism
chemical_list: C097503:CLC-5 chloride channel; D018118:Chloride Channels; D019275:Radiopharmaceuticals; D001613:beta 2-Microglobulin; D017263:Technetium Tc 99m Mertiatide; D019783:Technetium Tc 99m Dimercaptosuccinic Acid; D002945:Cisplatin