Local blood-to-tissue transport in Walker 256 metastatic brain tumors

Local blood-to-tissue transfer constants (K) in metastatic Walker 256 (WL-256) brain tumors produced by the intracarotid artery injection of WL-256 tumor cells in rats were measured using 14C-alpha-aminoisobutyric acid and quantitative autoradiography. Small compact and diffuse infiltrative intraparenchymal tumors had values of K similar to that of contralateral nontumorous brain tissue. Medium and large tumors, meningeal metastases and intraventricular tumors had higher K values (5 to 30 fold) than contralateral nontumorous brain tissue indicating that intraparenchymal tumor size and location in meningeal and choroidal tissue influence the permeability of tumor capillaries. The local intratumor values of K varied considerably in these tumors and this variability of K correlated to only a few specific histopathologic features of the tumors. The value of K abruptly decreased at the tumor-brain interface when this interface was sharply defined, indicating that the metastatic tumors have only a small effect on the permeability of adjacent brain capillaries. Low blood-to-tumor transport of water soluble drugs will significantly affect drug concentrations in the tumor and the tumor-drug exposure.