Figure 3.

Docetaxel pharmacokinetics and distribution to sites of disease development following inoculation of LCC6^WT-Luc cells via the o.t., i.c. and i.p. injection. 0.5, 1, 2, 4 and 24 hrs after i.v. injection of Dt (10 mg/kg) labeled with [³H]-Dt, animals (n = 4 per time point) were terminated by CO₂ asphyxiation and blood was collected by cardiac puncture and placed into an EDTA-containing micro-container placed on ice (see Materials and Methods). Subsequently plasma was separated from blood cells and the amount of [³H]-Dt in 50 mL of plasma was determined by liquid scintillation counting. These data were then used to calculate the plasma concentration of Dt (ng/mL) (A). Dt levels in ascites fluid (cell-associated and non-cell associated) were determined following a 5 mL lavage with serum media (see Materials and Methods). The total amount of fluid recovered from the peritoneal cavity was measured and an aliquot of the ascites was taken for scintillation counting. The amount of Dt per mL of ascites fluid was then determined (B). In animals inoculated with LCC6^WT-luc cells, tumors consistently developed in the pancreas. Therefore the pancreas from each mouse was harvested and processed (see Materials and Methods) for assessment of [³H]-Dt. These data were then used to estimate the amount of Dt in pancreatic tissue (ng/mg tissue). For mice bearing systemic disease, BLI data suggested that organs/tissues such as the brain, lung, rib cage and heart (F) exhibited tumor growth, however growth was most consistently observed in the adrenal glands and ovaries thus these organs were chosen as representative organs for metastatic disease. These tissues were collected and analyzed as described above (E). Similarly, tumors harvested from the animals bearing orthotopic tumors were collected and processed (D). All tissue levels were reported as ng Dt per mg wet tissue and the results presented represent the mean (n = 4) ±SD.