Histologic Assessment of Renal Toxicity in NIH Swiss Mice (22.5 ± 1.7 g) Given PT-RAIT
| TF10-pretargeted 90Y-IMP-288 dose ± gemcitabine | |||||||
|---|---|---|---|---|---|---|---|
| Score* | Buffer | Gemcitabine | 33.3 MBq | 25.9 MBq | 18.5 MBq | 25.9 MBq + gemcitabine† | 18.5 MBq + gemcitabine |
| 4 | — | — | — | — | — | — | — |
| 3 | 1‡ | 2§ | 1 | — | — | — | 1 |
| 2 | 1 | 1 | — | 1 | — | — | — |
| 1 | 14 | 3 | 10 | 8 | 6 | 5 | 7 |
| 0 | 5 | 5 | — | 2 | 5 | 5 | 3 |
↵* Kidney evaluation scores: 4, marked to severe tissue changes (>60% of kidney affected by interstitial lymphocytic infiltrates, glomerular mesangial thickening, and capillary basement membrane thickening or hydronephrosis); 3, moderate tissue changes (40%–60% of kidney affected by interstitial lymphocytic infiltrates, glomerular mesangial thickening, and capillary basement membrane thickening; hydronephrosis; or necrotizing arteriolitis); 2, mild tissue changes (20%–40% of kidney affected by interstitial lymphocytic infiltrates, glomerular mesangial thickening, and capillary basement membrane thickening or hydronephrosis); 1, minimal changes (<20% of kidney affected by interstitial lymphocytic infiltrates, glomerular mesangial thickening, and capillary basement membrane thickening); 0, normal tissue.
↵† Kidneys from animal removed at week 34.4 were not examined.
↵‡ Number of animals.
↵§ One of these animals was found dead at week 27.
Groups of mice (n = 11) received either PT-RAIT at week 0 or PT-RAIT at week 0 with 6 mg of gemcitabine given intraperitoneally at weeks 0, 1, and 2. PT-RAIT (33.3 MBq) treatment group started 2 wk after other groups and included additional group of age-matched buffer-control animals (n = 10). Animals were euthanized at week 36.