title: Assessment of renal function in mice with unilateral ureteral obstruction using 99mTc-MAG3 dynamic scintigraphy.
abstract: BACKGROUND
  Renal 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.
  
  
  METHODS
  UUO 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.
  
  
  RESULTS
  Compared 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Radiology and Vanderbilt University Institute of Imaging Science, Nashville, TN, USA.
authors.forename: Mohammed N
authors.initials: MN
authors.lastname: Tantawy
authors.forename: Rosie
authors.initials: R
authors.lastname: Jiang
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Keiko
authors.initials: K
authors.lastname: Takahashi
authors.forename: Todd E
authors.initials: TE
authors.lastname: Peterson
authors.forename: Dana
authors.initials: D
authors.lastname: Zemel
authors.forename: Chuan-Ming
authors.initials: CM
authors.lastname: Hao
authors.forename: Hiroki
authors.initials: H
authors.lastname: Fujita
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Harris
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Quarles
authors.forename: Takamune
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D007668:Kidney / Q000000981:diagnostic imaging* / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011866:Radioisotope Renography / Q000379:methods; D011877:Radionuclide Imaging / Q000379:methods; D019275:Radiopharmaceuticals; D017263:Technetium Tc 99m Mertiatide; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D014517:Ureteral Obstruction / Q000000981:diagnostic imaging* / Q000503:physiopathology
chemical_list: D019275:Radiopharmaceuticals; D017263:Technetium Tc 99m Mertiatide