Concurrent Measurements of Blood Flow and Transcapillary Transport in Xenotransplanted Human Gliomas in Immunosuppressed Rats2

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Abstract
Neonatal Fischer 344 rats were immunosuppressed with antithymocyte serum and later were given an injection intra-cerebrally 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 α-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.

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