VASCULAR-PERMEABILITY AND MICROCIRCULATION OF GLIOMAS AND MAMMARY CARCINOMAS TRANSPLANTED IN RAT AND MOUSE CRANIAL WINDOWS

Many brain tumors are highly resistant to chemotherapy, presumably due to the presence of a tight blood-tumor barrier. For a better understa nding of the regulation of this barrier by the brain environment, a ne w intravital microscopy model was established by transplanting tumor t issue into cranial windows in both rats and mice. The model was charac terized by RBC velocities, vessel diameters, and vascular permeabiliti es of various tumors: R3230AC (a rat mammary adenocarcinoma), MCaIV (a mouse mammary adenocarcinoma), and U87 and HGL21 (human malignant ast rocytomas). Our results showed that tumor blood flow in cranial window s was one to three orders of magnitude lower than the blood flow in pi al vessels and similar to that in dorsal skin-fold chambers observed i n previous studies. The mean vessel diameter ranged from 6.8 +/- 1.3 m u m for HGL21 to 30.4 +/- 8.5 mu m for MCaIV. At least one order of ma gnitude difference in vascular permeability to albumin was observed be tween tumor lines: 0.11 +/- 0.05x10(-7) cm/s for HGL21 versus 3.8 +/- 1.2x10(-7) cm/s for U87. The low vascular permeability of HGL21, which was also confirmed by both sodium fluorescein and Lissamine green inj ections, suggests that not all tumors are leaky to tracer molecules an d that the blood-tumor barrier of this tumor still possesses some char acteristics of blood-brain barrier as observed in other intracranial t umors. The model presented here will allow us to manipulate the vascul ar permeability in brain tumors and thus may provide new information o n the regulation of the blood-tumor barrier and new strategies for imp roving drug delivery in brain tumors.