Relationship of Renal Function in Mice to Strain, Sex and 177Lutetium-Somatostatin Receptor Ligand Treatment.

Abstract

Aim of the study was to establish parameters for 99mTc-MAG3 SPECT renal uptake kinetics in healthy SCID mice as a function of mouse strain and sex and to evaluate the feasibility of this method for detecting 177Lu-somatostatin receptor ligand (177Lu-SRL) treatment effects on kidney function. Dynamic semi-stationary SPECT acquisitions (68 frames, total duration 35 min) was started prior to i. v. injection of 99mTc-MAG3 in 12 female and 12male SCID mice. Additionally, 6 female SCID mice with neuroendocrine tumors were imaged 1-5 months after 177Lu-SRL (5 DOTATOC, 1 DOTA-JR11) treatment. Kidney function is expressed as maximum time to peak (Tmax), T50 and T25 in minutes (median [interquartile range]). Differences between groups were tested using the Mann-Whitney-U test, and SCID mouse parameters were compared with data for C57BL/6N mice from a recent publication. Significant sex-based differences in Tmax between strains were observed (females: C57BL/6N 1.6 [1.4-1.7], SCID 1.4 [1.3-1.5], p = 0.05; males: C57BL/6N 1.4 [1.3-1.4], SCID 1.6 [1.4-1.7], p = 0.04). In C57BL/6N mice, females showed a later Tmax (p < 0.01) than males. SCID mice showed no difference (p = 0.14). Treated SCID mice showed no significant delay in Tmax (2.0 [1.4-2.7], p = 0.15) but a significant delay in T50 (p = 0.02) and T25 (p = 0.01) compared to healthy untreated mice. This study demonstrated significant sex-related differences between SCID and C57BL/6N mouse strains in kidney function. Establishment of normal values for different strains and sexes therefore is important for experimental therapy studies. Renal SPECT imaging with 99mTc-MAG3 was sufficiently sensitive to detect 177Lu-SRL treatment toxic effects on kidney function in SCID mice.