Uptake and Distribution of 3H-Methotrexate by the Murine Ependymoblastoma

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Abstract
Steady-state 14C-inulin and 3H-methotrexate (MTX) plasma levels were maintained in nephrectomized C57BL/6 mice with an intracerebral (ic) glioma (or varying periods up to 3 hours for MTX and 6 hours for inulin. 3H-MTX tumor uptake was studied under 3 experimental conditions: 1) varying doses of MTX of 0.12 mM/kg, 1.4 mM/kg, and 42.8 mM/kg mouse; 2) low-dose MTX with citrovorum factor at a concentration 100-fold greater; and 3) a single quantitated injection of MTX. It was found that a) MTX distributed in a space almost identical to the inulin space in ic tumor; b) there was no difference in uptake or distribution of MTX in ic tumor, brain adjacent to tumor, or normal distant brain at the 3 dose levels of 3H-MTX used; c) the distant brain was relatively impermeable to MTX; d) the brain adjacent to tumor had a space between tumor and normal brain; e) citrovorum factor had no effect on the distribution space or equilibrium t½ for MTX in ic tumor; and f) 24 hours after a single injection of MTX and inulin, nearly 5 times (P = 0.001) more MTX than inulin was present in tumor.

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