Toxicity of pretargeted RIT in athymic mice
. | 0 μCi . | 1200 μCi (44.4 MBq) . | . | . | . | 200 μCi (7.4 MBq) . | . | |||
|---|---|---|---|---|---|---|---|---|---|---|
| Day . | Untreated Control . | CC49 (scFv)4-SA . | 1F5 Ab-SA . | 1F5 (scFv)4-SA . | B9E9 (scFv)4-SA . | DOTA-1F5 Ab, conventional . | P* . | |||
| WBCs, × 109/L | ||||||||||
| 0 | 8.4 ± 1.3 | 5.2 ± 0.9 | 4.6 ± 1.7 | 6.2 ± 1.4 | 6.0 ± 1.9 | 3.3 ± 1.5 | — | |||
| 7 | 6.8 ± 2.7 | 3.1 ± 1.4 | 3.5 ± 1.3 | 3.3 ± 1.2 | 3.4 ± 1.2 | 0.8 ± 0.6 | <.001 | |||
| 14 | 6.0 ± 1.7 | 5.6 ± 2.3 | 3.8 ± 1.9 | 5.4 ± 1.8 | 5.6 ± 2.6 | 1.4 ± 0.5 | .009 | |||
| 21 | 6.1 ± 1.1 | 7.2 ± 2.5 | 5.0 ± 1.1 | 7.0 ± 1.2 | 6.5 ± 2.6 | 3.8 ± 1.4 | .005 | |||
| Hgb, g/dL† | ||||||||||
| 0 | 15.2 ± 1.6 | 15.5 ± 0.4 | 15.2 ± 0.7 | 14.6 ± 1.2 | 16.2 ± 1.5 | 15.1 ± 1.5 | — | |||
| 7 | 14.6 ± 1.7 | 15.3 ± 0.3 | 15.0 ± 0.7 | 13.4 ± 1.8 | 14.6 ± 0.6 | 11.2 ± 2.0 | — | |||
| 14 | 14.7 ± 1.5 | 15.3 ± 1.0 | 13.9 ± 2.1 | 14.2 ± 1.5 | 15.3 ± 1.3 | 7.8 ± 2.6 | <.001 | |||
| 21 | 15.0 ± 0.4 | 15.3 ± 1.2 | 15.2 ± 1.7 | 14.8 ± 0.9 | 15.4 ± 0.3 | 13.0 ± 1.5 | — | |||
| Platelets, × 109/L | ||||||||||
| 0 | 1411 ± 303 | 1522 ± 96 | 1270 ± 344 | 1198 ± 199 | 1414 ± 164 | 1288 ± 102 | — | |||
| 7 | 1165 ± 282 | 1561 ± 327 | 1157 ± 145 | 1054 ± 172 | 1398 ± 557 | 733 ± 113 | .005 | |||
| 14 | 1561 ± 356 | 1707 ± 448 | 1239 ± 250 | 948 ± 192 | 1285 ± 463 | 880 ± 275 | — | |||
| 21 | 1173 ± 187 | 1650 ± 621 | 1298 ± 267 | 1092 ± 145 | 1278 ± 413 | 1153 ± 185 | — | |||
. | 0 μCi . | 1200 μCi (44.4 MBq) . | . | . | . | 200 μCi (7.4 MBq) . | . | |||
|---|---|---|---|---|---|---|---|---|---|---|
| Day . | Untreated Control . | CC49 (scFv)4-SA . | 1F5 Ab-SA . | 1F5 (scFv)4-SA . | B9E9 (scFv)4-SA . | DOTA-1F5 Ab, conventional . | P* . | |||
| WBCs, × 109/L | ||||||||||
| 0 | 8.4 ± 1.3 | 5.2 ± 0.9 | 4.6 ± 1.7 | 6.2 ± 1.4 | 6.0 ± 1.9 | 3.3 ± 1.5 | — | |||
| 7 | 6.8 ± 2.7 | 3.1 ± 1.4 | 3.5 ± 1.3 | 3.3 ± 1.2 | 3.4 ± 1.2 | 0.8 ± 0.6 | <.001 | |||
| 14 | 6.0 ± 1.7 | 5.6 ± 2.3 | 3.8 ± 1.9 | 5.4 ± 1.8 | 5.6 ± 2.6 | 1.4 ± 0.5 | .009 | |||
| 21 | 6.1 ± 1.1 | 7.2 ± 2.5 | 5.0 ± 1.1 | 7.0 ± 1.2 | 6.5 ± 2.6 | 3.8 ± 1.4 | .005 | |||
| Hgb, g/dL† | ||||||||||
| 0 | 15.2 ± 1.6 | 15.5 ± 0.4 | 15.2 ± 0.7 | 14.6 ± 1.2 | 16.2 ± 1.5 | 15.1 ± 1.5 | — | |||
| 7 | 14.6 ± 1.7 | 15.3 ± 0.3 | 15.0 ± 0.7 | 13.4 ± 1.8 | 14.6 ± 0.6 | 11.2 ± 2.0 | — | |||
| 14 | 14.7 ± 1.5 | 15.3 ± 1.0 | 13.9 ± 2.1 | 14.2 ± 1.5 | 15.3 ± 1.3 | 7.8 ± 2.6 | <.001 | |||
| 21 | 15.0 ± 0.4 | 15.3 ± 1.2 | 15.2 ± 1.7 | 14.8 ± 0.9 | 15.4 ± 0.3 | 13.0 ± 1.5 | — | |||
| Platelets, × 109/L | ||||||||||
| 0 | 1411 ± 303 | 1522 ± 96 | 1270 ± 344 | 1198 ± 199 | 1414 ± 164 | 1288 ± 102 | — | |||
| 7 | 1165 ± 282 | 1561 ± 327 | 1157 ± 145 | 1054 ± 172 | 1398 ± 557 | 733 ± 113 | .005 | |||
| 14 | 1561 ± 356 | 1707 ± 448 | 1239 ± 250 | 948 ± 192 | 1285 ± 463 | 880 ± 275 | — | |||
| 21 | 1173 ± 187 | 1650 ± 621 | 1298 ± 267 | 1092 ± 145 | 1278 ± 413 | 1153 ± 185 | — | |||
Serial measurements of leukocyte counts (WBC), hemoglobin (Hgb), and platelets were made in untreated control mice or in mice treated with either 200 μCi of directly radiolabeled 90Y-DOTA-1F5 Ab or 1200 μCi 90Y-DOTA-biotin following pretargeting with 1F5 (scFv)4-SA, B9E9 (scFv)4-SA, control CC49 (scFv)4-SA, or 1F5 Ab-SA chemical conjugate. Data represent mean (n = 10) plus or minus the standard deviation (SD).
—indicates not significant.
P values are representative of significant differences between the 1F5 (scFv)4-SA fusion protein and directly labeled DOTA-1F5 Ab.
For Hgb conversion to Sl units (g/L), multiply the given values by a factor of 10.