The intracerebral penetration of intraventricularly administered methotrexate: A quantitative autoradiographic study

Abstract

The local concentration and distribution of methotrexate following intraventricular administration were studied in the brains of New Zealand White rabbits. Tritiated methotrexate was injected through subcutaneous reservoirs connected to ventricular catheters, the animals were sacrificed one hour after administration of the drug, and the distribution of the radiolabelled compound was assessed using quantitative autoradiographic techniques. The intracerebral distribution of tritiated inulin delivered in an identical fashion was studied for comparison. One hour after intraventricular administration of radiolabelled methotrexate or inulin approximately 40% of the area of the brain sections contained appreciable concentrations of the radiolabelled tracer. Gray matter adjacent to the cerebrospinal fluid, including the hippocampus, thalamus, caudate nucleus, and periaquaductal gray contained the highest concentrations of 3H-methotrexate. Large white matter tracts contained smaller amounts of tracer activity. The rapid and extensive penetration of intraventricularly administered methotrexate and inulin into normal brain parenchyma and the high methotrexate concentrations in specific regions of the brain provide insight into the pathogenesis of methotrexate-induced neurotoxicity.

Central Nervous System Prophylaxis in Non-Hodgkin Lymphoma: Who, What, and When?

“…Increasingly, CNS-penetrating doses of antimetabolites such as MTX and cytarabine are being used to prevent, or pre-emptively treat, CNS infiltration. This approach has theoretical appeal as IT MTX likely fails to achieve therapeutic concentrations in brain parenchyma [97]. Five studies supporting the efficacy of systemic MTX/cytarabine have been performed to our knowledge ( Table 2).…”

Meningeal Carcinomatosis: A Metastasis from Gastroesophageal Junction Adenocarcinoma

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“…Chemotherapy given intrathecally penetrates only a few millimeters into the brain or bulky leptomeningeal tumors. 164,165 Therefore, a tumor that can be visualized on MRI, such as enhancing nodules greater than a few millimeters in diameter, cannot be adequately treated by intrathecal chemotherapy and should first be treated with RT.…”