Abstract
BackgroundRenal scintigraphy using 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) is widely used for the assessment of renal function in humans. However, the application of this method to animal models of renal disease is currently limited, especially in rodents. Here, we have applied 99mTc-MAG3 renal scintigraphy to a mouse model of unilateral ureteral obstruction (UUO) and evaluated its utility in studying obstructive renal disease.MethodsUUO mice were generated by complete ligation of the left ureter. Sham-operated mice were used as a control. Renal function was investigated on days 0, 1, 3, and 6 post-surgery using dynamic planar imaging of 99mTc-MAG3 activity following retro-orbital injection. Time-activity curves (TACs) were produced for individual kidneys and renal function was assessed by 1) the slope of initial 99mTc-MAG3 uptake (SIU), which is related to renal perfusion; 2) peak activity; and 3) the time-to-peak (TTP). The parameters of tubular excretion were not evaluated in this study as 99mTc-MAG3 is not excreted from UUO kidneys.ResultsCompared to sham-operated mice, SIU was remarkably (>60%) reduced in UUO kidneys at day 1 post surgery and the TACs plateaued, indicating that 99mTc-MAG3 is not excreted in these kidneys. The plateau activity in UUO kidneys was relatively low (~40% of sham kidney’s peak activity) as early as day1 post surgery, demonstrating that uptake of 99mTc-MAG3 is rapidly reduced in UUO kidneys. The time to plateau in UUO kidneys exceeded 200 sec, suggesting that 99mTc-MAG3 is slowly up-taken in these kidneys. These changes advanced as the disease progressed. SIU, peak activity and TTPs were minimally changed in contra-lateral kidneys during the study period.ConclusionsOur data demonstrate that renal uptake of 99mTc-MAG3 is remarkably and rapidly reduced in UUO kidneys, while the changes are minimal in contra-lateral kidneys. The parametric analysis of TACs suggested that renal perfusion as well as tubular uptake is reduced in UUO kidneys. This imaging technique should allow non-invasive assessments of UUO renal injury and enable a more rapid interrogation of novel therapeutic agents and protocols.
Highlights
Renal scintigraphy using 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) is widely used for the assessment of renal function in humans
Our data demonstrate that renal uptake of 99mTc-MAG3 is remarkably and rapidly reduced in ureteral obstruction (UUO) kidneys as early as day 1 post-surgery, while it is minimally changed in contralateral kidneys
The parametric analysis of time-activity curves (TACs) suggested that renal perfusion as well as tubular uptake is reduced in UUO kidneys
Summary
Renal scintigraphy using 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) is widely used for the assessment of renal function in humans. Renal scintigraphy or renograms using 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) is widely used for the assessment of renal function in humans, especially for the evaluation of postoperative complications in renal transplant recipients [1]. This radiotracer is extracted from the kidneys with high efficiency through secretion from proximal tubules [2,3]. The measurement of intrarenal 99mTc-MAG3 kinetics provides a minimally invasive, simple, and quantitative test of renal function, which does not require blood or urine sampling Given these features, 99mTc-MAG3 renography could serve as a useful tool for the repetitive and longitudinal assessment of renal function in pre-clinical animal models of renal disease. Quantitative analysis and longitudinal investigation of 99mTc-MAG3 renograms have not been carried out in animals with unilateral ureteral obstruction (UUO)
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