The DNA isolation and PBD-dimer recovery in tumor and major organs of WSU-DLCL2 xenograft mice after a single 5 mg/kg i.v. dose of anti-CD22 cyclobutyl-containing disulfide PBD-dimer and anti-CD22 cyclopropyl-containing disulfide PBD-dimer ADCs (1 and 2) (n = 2)
| ADC | Time | Extracted DNA | Recovered PBD-dimer 3 | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Tumor | Liver | Kidney | Lung | Tumor | Liver | Kidney | Lung | ||
| hours | mg/g tissue | pmol/g tissue | |||||||
| Cyclobutyl-containing ADC 1 | 24 | 5.13 | 2.20 | 2.07 | 1.20 | 63.6 | 2.80 | <LLOQ | <LLOQ |
| 5.80 | 2.07 | 1.87 | 2.60 | 83.7 | 2.80 | <LLOQ | 3.20 | ||
| 96 | 4.87 | 2.47 | 1.60 | 1.67 | 277 | 2.33 | <LLOQ | 3.07 | |
| 2.73 | 2.07 | 1.93 | 2.00 | 192 | 3.87 | <LLOQ | 2.60 | ||
| Cyclopropyl-containing ADC 2 | 24 | 7.33 | 2.00 | 2.00 | 1.87 | 3.33 | ND | ND | ND |
| 5.53 | 1.87 | 1.33 | 1.67 | <LLOQ | ND | ND | ND | ||
| 96 | 8.33 | 2.07 | 2.00 | 2.00 | 3.33 | ND | ND | ND | |
| 5.93 | 2.00 | 2.00 | 1.13 | 5.73 | ND | ND | ND | ||
ND, not detected. DNA was isolated from 15 mg of tissue homogenates. Less than 0.01 µg DNA could be extracted from 15 µl of plasma sample, but no PBD-dimer 3 was detected after enzyme digestion and heating. LLOQ, 0.030 pmol for PBD-dimer 3 after DNA digestion.