Intraneoplastic injection of methotrexate for experimental brain-tumor chemotherapy

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Abstract
The retention and distribution of 3H-methotrexate (MTX-3H) after direct intracerebral or intraneoplastic injection were studied in mice bearing subcutaneous or intracerebral ependymoblastomas. After intracerebral injection of MTX-3H in nontumor-bearing animals, a large amount of the drug was retained in the head, much more than could have been retained after systemic administration, and there was rapid spreading of the drug through the ipsilateral hemisphere. Intraneoplastic injection of subcutaneous and intracerebral tumors produced rapid spreading of the drug through the tumors. Initially, the drug was in the interstitial fluid of the tumors followed by earlier cellular uptake than was seen after i.v. injection. Even though the distribution of the drug in the intracerebral tumors was not uniform, and some intracranial tumor deposits contained less radioactivity than areas closer to the site of injection, intraneoplastic injection may have advantages for brain tumor chemotherapy. Further experimental study is necessary before clinical application can be recommended, especially evaluation of neurotoxicity after intracerebral, intraneoplastic injection of MTX or other chemotherapeutic agents.