Blood tumor permeability of experimental brain tumor: an electron microscopic study using lanthanum

In an attempt to assess the permeability of microvessels in the experimental brain tumor model, lanthanum ion (La3+) was used as a low-molecular weight electron microscopic probe. Rat glioma 9 L and adenocarcinoma ACL15 were transplanted to the brain and subflank of rats. The rats were then anesthetized sequentially perfused with saline, saline plus La3+ followed by a fixative in phosphate buffer. The brain and subcutaneous tumors were removed, further fixed, and processed for electron microscopy. La3 did not pass through the tight junctions of the normal cerebral endothelium. Similarly, La3+ did not penetrate the endothelial cell wall of the microvessels in the transplanted brain tumors. In contrast, extravasation of La3+ from the microvessels in the transplanted subcutaneous tumors was observed. The electron microscopy examination results indicate that the vesicular transport was a predominant mechanism in the penetration of La3+ through the endothelial cell wall. Since most chemotherapeutic agents similar as La3+ are of low molecular weight, we can suggest from the results of our present study that the blood tumor permeability of the anti-cancer agents in the rat model of brain glioma transplantation differs from that in the rat model of subcutaneous glioma transportation. In other words, our results indicate that when the subcutaneous glioma transplantation model is used in sensitivity tests of anti-cancer agents, it will possibly be very difficult to predict the anti-neoplastic effect in vivo.