The limited effect of
chemotherapy on malignant
brain tumors has been related to
tumor cell insensitivity to the drugs and to their ineffectual delivery to the
tumor. The studies by Groothuis and Neuwelt et al have shown that the studies of
tumor vessel permeability show considerable variability in different areas of
tumors and between different
tumor models. The present studies used the 9L
gliosarcoma model in Fischer 344 rats to evaluate the increase of
tumor vessel permeability by osmotic BBB opening on
drug delivery to the
tumor, brain adjacent to
tumor (BAT), and brain distant to
tumor using
cis-diamminedichloroplatinum (CDDP) as a chemotherapeutic agent which was water soluble and rarely permeable to BBB. In addition the difference of delivery to normal brain and
tumor tissue were studied on intravenous or intracarotid administration of
cisplatin with or without intracarotid infusion of graded (20%, 25%) hyperosmolar
mannitol.
Evans blue, which binds to
plasma albumin, was used to provide a visual marker of BBB opening. 20% or 25% hyperosmolar
mannitol infusion to right internal carotid artery for BBB disruption was done at 0.12 ml/sec for 30 sec with controlled respiration after temporally clipping of right common carotid artery. Then
cis-diamminedichloroplatinum (CDDP) was infused at 0.5 mg/ml/100 gr (
body weight). In control studies isotonic saline instead of
mannitol was infused to intracarotid artery at identical rate and volume. In 14 9L
gliosarcoma bearing rats and 3 normal rats
cis-diamminedichloroplatinum (CDDP) delivery to
tumor and normal brain.(ABSTRACT TRUNCATED AT 250 WORDS)