Figure 2. Variable penetration of paclitaxel into experimental 231-BR brain metastases of breast cancer.
A-C, Mice were inoculated with EGFP tagged 231-BR-HER2 brain-tropic tumor cells, and permitted to develop metastases. Before necropsy, mice were injected with 3kDa Texas Red dextran (B) or 14C-Paclitaxel (C), and free drug was then perfused from the vasculature. A single section of brain was imaged for metastases (EGFP, A), Texas Red Dextran uptake (B) and imaged for 14C-paclitaxel uptake. Variability is noted within and between lesions. D, The fold-uptake of paclitaxel relative to normal brain was determined for 379 experimental metastases. Only 9.8% of lesions demonstrated >50-fold greater drug uptake as compared to normal brain, while 14% of lesions were statistically indistinct from normal brain. In experiments not shown, paclitaxel only caused cytotoxicity in the 9.8% of freely permeable lesions. E, Paclitaxel distribution over time in experimental metastases (purple) versus systemic lesions and normal brain. While drug uptake is higher in experimental metastases than normal brain, it remains logs below systemic lesions. Adapted from Lockman, et al. (26).