RETENTION OF TRITIATED METHOTREXATE IN A TRANSPLANTABLE MOUSE GLIOMA

  • 1 January 1976
    • journal article
    • research article
    • Vol. 36  (9) , 3058-3066
Abstract
The uptake and distribution of 3H-methotrexate ([3H]MTX) were studied by autoradiography and liquid scintillation counting for up to 7 days after i.v. injection in mice bearing s.c. or intracerebral (i.c.) implants of a transplantable mouse ependymoblastoma. Autoradiography showed that s.c. tumors took up more [3H]MTX than i.c. tumors. In s.c. and i.c. tumors, [3H]MTX was intracellular, with very little in interstitial fluid sites. Retention of [3H]MTX gradually diminished with time, with some still being present 7 days after injection. The distribution of [3H]MTX in the i.c. tumors was not uniform, and portions of these tumors were relatively inaccessible to the drug. The uniformity of distribution did not improve with time. Scintillation counting showed that s.c. tumors accumulated less [3H]MTX and retained a lower proportion of [3H]MTX than many normal tissues. These studies indicate that [3H]MTX has 3 major shortcomings as a chemotherapeutic agent for brain tumors. The amount of drug taken up by the transplantable mouse ependymoblastoma was small in comparison with normal tissues and in comparison with other agents taken up by this tumor. The distribution of the drug in the i.c. tumors was nonuniform, with tumor cells in certain areas remaining relatively inaccessible to the drug. Retention of the drug in the tumor was less than in normal tissues.