Table 1.
Pharmacokinetic characteristics of 86Y-CHX-A″-DTPA-panitumumab injected i.v. via tail vein of female athymic (NCr) nu/nu mice bearing LS-174T, PC-3 and A431 tumor xenografts. Data represent the mean values from three to six determinations.
| Pharmacokinetic characteristics | LS174T (Colorectal) | PC-3 (Prostate) | A431 (Epidermoid) |
|---|---|---|---|
| Relative in vitro expression# | 62.5 | 150.9 | 2072.2 |
| Relative in vivo expression | + | +−++ | +++ |
| Blood clearance (h) | |||
| α-t1/2 | 3.7 ± 1.7 | 2.7 ± 1.2 | 3.1 ± 1.3 |
| β-t1/2 | 58.4 ± 15.3 | 69.2 ± 14.4 | 73.9 ± 13.0 |
| Blood AUC[0→4] (%ID.d.g−1) | 31.4 ± 1.5 | 30.0 ± 2.2 | 32.3 ± 2.2 |
| Tumor AUC[0→4] (%ID.d.g−1) | 96.8 ± 5.6 | 61.1 ± 3.7 | 65.3 ± 3.2 |
| Tumor PET AUC[0→3] (%ID.d.cc−1) | 72.4 ± 5.3 | 38.8 ± 2.8 | 51.2 ± 2.9 |
| Tumor PET AUC[0→3] (%ID.d.cc−1)* | 23.2 ± 3.7 | 21.7 ± 1.0 | 26.3 ± 1.9 |
| Tumor AUC[0→4]: Blood AUC[0→4] | 3.1 | 2.0 | 2.0 |
| Tumor AUMC[0→4] (%ID.d2.g−1) | 262.5 ± 14.9 | 171.9 ± 10.3 | 179.9 ± 8.8 |
| Tumor MRT (d) | 2.7 | 2.8 | 2.7 |
#
Mean fluorescence intensity from flow cytometry cell binding studies as a measure of relative in vitro expression. Data adapted from Ray GL et al. (41).
*
Receptor blocking studies performed by co-injecting 0.1 mg panitumumab with the radiotracer. Values obtained from the blocking studies were significantly lower than the unblocked studies ((p < 0.05) demonstrating receptor-mediated accumulation in the tumors.