Concurrent measurements of blood flow and transcapillary transport in xenotransplanted human gliomas in immunosuppressed rats.

Neonatal Fischer 344 rats were immunosuppressed with antithymocyte serum and later were given an injection intracerebrally of cells from the human glioma permanent line D-54MG. Symptomatic tumor-bearing rats were studied with double-label quantitative autoradiography to concurrently measure blood flow and a unidirectional blood-to-tissue transfer constant (K) for alpha-aminoisobutyric acid (AIB). A net extraction fraction (En) was calculated from the measured values for blood flow and K. Mean whole tumor blood flow was 53.5 +/- 4.9 ml/100 g/min (mean +/- SEM), which was significantly less than the blood flow to the tumor-free cortex (198 +/- 15.5 ml/100 g/min) but not significantly different from the blood flow in the tumor-free corpus callosum (50.6 +/- 4.3 ml/100 g/min). Mean whole tumor K-value for AIB was 5.8 +/- 0.5 ml/100 g/min, approximately 30 times the K-value for tumor-free brain. The calculated mean whole tumor En was 0.2 +/- 0.09, nearly 100 times the value for the tumor-free brain. Regionally, blood flow was lower in the tumor center and higher in its tumor periphery, although the difference was not significant. Both K- and En-values were significantly higher for the tumor center and decreased radially for the areas from center out. The values for K and En of AIB in the D-54MG gliomas are the highest of any experimental brain tumor model studied to date and indicate that in some tumor regions in this model, blood-to-tissue transport of the water-soluble compound AIB may be dependent on blood flow as well as on the permeability-surface area product of the tumor capillaries.