Toxicity of pretargeted RIT in athymic mice
| . | Day . | Control . | 1F5-SA . | BC8-SA . | ||||
|---|---|---|---|---|---|---|---|---|
| — . | 200 μCi . | 400 μCi . | 800 μCi . | 200 μCi . | 400 μCi . | 800 μCi . | ||
| WBC (1000/μL) | 0 | 6.0 ± 0.9 | 5.3 ± 0.8 | 7.0 ± 0.4 | 6.5 ± 1.4 | 5.8 ± 0.3 | 6.2 ± 0.7 | 6.7 ± 1.4 |
| 7 | 5.9 ± 1.3 | 4.7 ± 1.1 | 5.2 ± 1.0 | 5.3 ± 1.3 | 2.9 ± 1.7 | 5.3 ± 0.8 | 4.8 ± 1.6 | |
| 14 | 4.5 ± 1.0 | 3.8 ± 0.5 | 3.4 ± 0.9 | 4.7 ± 2.6 | 5.4 ± 1.8 | 6.7 ± 0.8 | 4.5 ± 1.0 | |
| 21 | 7.2 ± 2.2 | 5.6 ± 2.3 | 5.3 ± 1.0 | 5.9 ± 1.9 | 7.0 ± 1.2 | 8.5 ± 2.0 | 5.6 ± 0.6 | |
| Hgb (g/dL) | 0 | 14.1 ± 1.2 | 14.0 ± 1.9 | 13.6 ± 2.2 | 13.7 ± 2.4 | 13.2 ± 2.0 | 14.3 ± 1.1 | 13.2 ± 2.0 |
| 7 | 13.8 ± 1.3 | 13.8 ± 0.7 | 12.4 ± 1.6 | 12.2 ± 1.4 | 14.1 ± 0.9 | 14.4 ± 0.6 | 12.2 ± 2.1 | |
| 14 | 13.4 ± 0.4 | 13.5 ± 1.8 | 13.2 ± 1.7 | 12.5 ± 2.1 | 13.1 ± 0.9 | 13.9 ± 0.7 | 14.8 ± 1.6 | |
| 21 | 13.3 ± 0.8 | 14.1 ± 0.9 | 13.8 ± 0.7 | 14.2 ± 0.6 | 13.7 ± 0.9 | 14.5 ± 0.4 | 14.0 ± 0.5 | |
| Platelets (1000/μL) | 0 | 1190 ± 149 | 1004 ± 61.5 | 1104 ± 135 | 1152 ± 188 | 1198 ± 199 | 1150 ± 201 | 1078 ± 49.7 |
| 7 | 1063 ± 136 | 961 ± 109 | 872 ± 121 | 775 ± 144 | 954 ± 172 | 990 ± 161 | 624 ± 142 | |
| 14 | 962 ± 56.1 | 845 ± 169 | 777 ± 192 | 718 ± 117 | 748 ± 192 | 970 ± 178 | 730 ± 175 | |
| 21 | 1038 ± 186 | 1076 ± 150 | 825 ± 186 | 995 ± 100 | 892 ± 145 | 1011 ± 171 | 1067 ± 158 | |
| AST (IU/L) | 0 | 147 ± 94.0 | 211 ± 95.1 | 197 ± 91.0 | 166 ± 92.9 | 164 ± 92.6 | 171 ± 98.1 | 188 ± 91.2 |
| 7 | 166 ± 79.5 | 255 ± 89.3 | 290 ± 100 | 316 ± 102 | 176 ± 88.0 | 220 ± 96.5 | 302 ± 79.8 | |
| 14 | 181 ± 29.9 | 248 ± 54.8 | 215 ± 97.7 | 322 ± 80.8 | 241 ± 96.0 | 192 ± 89.0 | 241 ± 94.6 | |
| 21 | 212 ± 62.2 | 248 ± 45.3 | 190 ± 67.2 | 355 ± 40.8 | 176 ± 47.1 | 171 ± 79.6 | 317 ± 88.0 | |
| ALT (IU/L) | 0 | 117 ± 84.2 | 155 ± 85.0 | 88.5 ± 47.8 | 115 ± 73.2 | 101 ± 58.0 | 79.6 ± 45.8 | 99 ± 62.0 |
| 7 | 83.0 ± 61.7 | 172 ± 72.3 | 104 ± 82.0 | 217 ± 71.4 | 148 ± 61.2 | 99.2 ± 61.1 | 191 ± 55.9 | |
| 14 | 71.8 ± 31.9 | 128 ± 57.5 | 150 ± 67.9 | 149 ± 77.0 | 93.0 ± 55.7 | 53.5 ± 26.5 | 63.5 ± 34.2 | |
| 21 | 67.5 ± 15.9 | 84.6 ± 31.7 | 121 ± 81.9 | 73.3 ± 34.8 | 72.5 ± 46.1 | 77.7 ± 50.4 | 60.6 ± 22.1 | |
| Creatinine (mg/dL) | 0 | 0.40 ± 0.1 | 0.30 ± 0.1 | 0.33 ± 0.2 | 0.33 ± 0.1 | 0.29 ± 0.1 | 0.33 ± 0.1 | 0.20 ± 0.1 |
| 7 | 0.22 ± 0.1 | 0.34 ± 0.1 | 0.21 ± 0.1 | 0.22 ± 0.1 | 0.22 ± 0.1 | 0.26 ± 0.1 | 0.24 ± 0.1 | |
| 14 | 0.25 ± 0.1 | 0.22 ± 0.1 | 0.20 ± 0.1 | 0.24 ± 0.1 | 0.24 ± 0.1 | 0.35 ± 0.1 | 0.35 ± 0.1 | |
| 21 | 0.30 ± 0.1 | 0.24 ± 0.1 | 0.27 ± 0.1 | 0.34 ± 0.1 | 0.32 ± 0.1 | 0.30 ± 0.1 | 0.41 ± 0.2 | |
| Weight (g) | 0 | 23.4 ± 1.8 | 23.0 ± 1.3 | 22.5 ± 1.9 | 22.9 ± 2.6 | 22.2 ± 1.7 | 23.4 ± 1.4 | 22.8 ± 1.8 |
| 7 | 25.0 ± 1.7 | 23.5 ± 1.4 | 23.5 ± 2.5 | 23.3 ± 2.5 | 22.6 ± 1.4 | 24.5 ± 1.3 | 22.9 ± 1.2 | |
| 14 | 24.9 ± 2.1 | 23.3 ± 1.5 | 23.3 ± 1.5 | 24.6 ± 2.4 | 23.1 ± 1.6 | 25.3 ± 0.9 | 23.7 ± 1.0 | |
| 21 | 24.8 ± 2.1 | 23.4 ± 2.1 | 23.4 ± 1.2 | 24.6 ± 2.2 | 23.7 ± 1.6 | 25.7 ± 1.6 | 23.8 ± 0.8 | |
| . | Day . | Control . | 1F5-SA . | BC8-SA . | ||||
|---|---|---|---|---|---|---|---|---|
| — . | 200 μCi . | 400 μCi . | 800 μCi . | 200 μCi . | 400 μCi . | 800 μCi . | ||
| WBC (1000/μL) | 0 | 6.0 ± 0.9 | 5.3 ± 0.8 | 7.0 ± 0.4 | 6.5 ± 1.4 | 5.8 ± 0.3 | 6.2 ± 0.7 | 6.7 ± 1.4 |
| 7 | 5.9 ± 1.3 | 4.7 ± 1.1 | 5.2 ± 1.0 | 5.3 ± 1.3 | 2.9 ± 1.7 | 5.3 ± 0.8 | 4.8 ± 1.6 | |
| 14 | 4.5 ± 1.0 | 3.8 ± 0.5 | 3.4 ± 0.9 | 4.7 ± 2.6 | 5.4 ± 1.8 | 6.7 ± 0.8 | 4.5 ± 1.0 | |
| 21 | 7.2 ± 2.2 | 5.6 ± 2.3 | 5.3 ± 1.0 | 5.9 ± 1.9 | 7.0 ± 1.2 | 8.5 ± 2.0 | 5.6 ± 0.6 | |
| Hgb (g/dL) | 0 | 14.1 ± 1.2 | 14.0 ± 1.9 | 13.6 ± 2.2 | 13.7 ± 2.4 | 13.2 ± 2.0 | 14.3 ± 1.1 | 13.2 ± 2.0 |
| 7 | 13.8 ± 1.3 | 13.8 ± 0.7 | 12.4 ± 1.6 | 12.2 ± 1.4 | 14.1 ± 0.9 | 14.4 ± 0.6 | 12.2 ± 2.1 | |
| 14 | 13.4 ± 0.4 | 13.5 ± 1.8 | 13.2 ± 1.7 | 12.5 ± 2.1 | 13.1 ± 0.9 | 13.9 ± 0.7 | 14.8 ± 1.6 | |
| 21 | 13.3 ± 0.8 | 14.1 ± 0.9 | 13.8 ± 0.7 | 14.2 ± 0.6 | 13.7 ± 0.9 | 14.5 ± 0.4 | 14.0 ± 0.5 | |
| Platelets (1000/μL) | 0 | 1190 ± 149 | 1004 ± 61.5 | 1104 ± 135 | 1152 ± 188 | 1198 ± 199 | 1150 ± 201 | 1078 ± 49.7 |
| 7 | 1063 ± 136 | 961 ± 109 | 872 ± 121 | 775 ± 144 | 954 ± 172 | 990 ± 161 | 624 ± 142 | |
| 14 | 962 ± 56.1 | 845 ± 169 | 777 ± 192 | 718 ± 117 | 748 ± 192 | 970 ± 178 | 730 ± 175 | |
| 21 | 1038 ± 186 | 1076 ± 150 | 825 ± 186 | 995 ± 100 | 892 ± 145 | 1011 ± 171 | 1067 ± 158 | |
| AST (IU/L) | 0 | 147 ± 94.0 | 211 ± 95.1 | 197 ± 91.0 | 166 ± 92.9 | 164 ± 92.6 | 171 ± 98.1 | 188 ± 91.2 |
| 7 | 166 ± 79.5 | 255 ± 89.3 | 290 ± 100 | 316 ± 102 | 176 ± 88.0 | 220 ± 96.5 | 302 ± 79.8 | |
| 14 | 181 ± 29.9 | 248 ± 54.8 | 215 ± 97.7 | 322 ± 80.8 | 241 ± 96.0 | 192 ± 89.0 | 241 ± 94.6 | |
| 21 | 212 ± 62.2 | 248 ± 45.3 | 190 ± 67.2 | 355 ± 40.8 | 176 ± 47.1 | 171 ± 79.6 | 317 ± 88.0 | |
| ALT (IU/L) | 0 | 117 ± 84.2 | 155 ± 85.0 | 88.5 ± 47.8 | 115 ± 73.2 | 101 ± 58.0 | 79.6 ± 45.8 | 99 ± 62.0 |
| 7 | 83.0 ± 61.7 | 172 ± 72.3 | 104 ± 82.0 | 217 ± 71.4 | 148 ± 61.2 | 99.2 ± 61.1 | 191 ± 55.9 | |
| 14 | 71.8 ± 31.9 | 128 ± 57.5 | 150 ± 67.9 | 149 ± 77.0 | 93.0 ± 55.7 | 53.5 ± 26.5 | 63.5 ± 34.2 | |
| 21 | 67.5 ± 15.9 | 84.6 ± 31.7 | 121 ± 81.9 | 73.3 ± 34.8 | 72.5 ± 46.1 | 77.7 ± 50.4 | 60.6 ± 22.1 | |
| Creatinine (mg/dL) | 0 | 0.40 ± 0.1 | 0.30 ± 0.1 | 0.33 ± 0.2 | 0.33 ± 0.1 | 0.29 ± 0.1 | 0.33 ± 0.1 | 0.20 ± 0.1 |
| 7 | 0.22 ± 0.1 | 0.34 ± 0.1 | 0.21 ± 0.1 | 0.22 ± 0.1 | 0.22 ± 0.1 | 0.26 ± 0.1 | 0.24 ± 0.1 | |
| 14 | 0.25 ± 0.1 | 0.22 ± 0.1 | 0.20 ± 0.1 | 0.24 ± 0.1 | 0.24 ± 0.1 | 0.35 ± 0.1 | 0.35 ± 0.1 | |
| 21 | 0.30 ± 0.1 | 0.24 ± 0.1 | 0.27 ± 0.1 | 0.34 ± 0.1 | 0.32 ± 0.1 | 0.30 ± 0.1 | 0.41 ± 0.2 | |
| Weight (g) | 0 | 23.4 ± 1.8 | 23.0 ± 1.3 | 22.5 ± 1.9 | 22.9 ± 2.6 | 22.2 ± 1.7 | 23.4 ± 1.4 | 22.8 ± 1.8 |
| 7 | 25.0 ± 1.7 | 23.5 ± 1.4 | 23.5 ± 2.5 | 23.3 ± 2.5 | 22.6 ± 1.4 | 24.5 ± 1.3 | 22.9 ± 1.2 | |
| 14 | 24.9 ± 2.1 | 23.3 ± 1.5 | 23.3 ± 1.5 | 24.6 ± 2.4 | 23.1 ± 1.6 | 25.3 ± 0.9 | 23.7 ± 1.0 | |
| 21 | 24.8 ± 2.1 | 23.4 ± 2.1 | 23.4 ± 1.2 | 24.6 ± 2.2 | 23.7 ± 1.6 | 25.7 ± 1.6 | 23.8 ± 0.8 | |
Hematologic, hepatic, and renal toxicities and weight as assessment of general health in untreated control mice or mice treated with 200, 400, or 800 μCi (7.4, 14.8, or 29.6 MBq) radiolabeled DOTA-biotin and pretargeted BC8-SA or IF5-SA conjugate.