Retention of tritiated methotrexate in a transplantable mouse glioma.
The uptake and distribution of tritiated methotrexate ([H]MTX) were studied by autoradiography and liquid scintillation countinf 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 both s.c. and i.c. tumors, [3H]MTX was mainly intracellular, with very little in intersitial 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 much less [3H-A1MTX 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. First, 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. Second, the distribution of the drug in the i.c. tumors was nonuniform, with tumor cells in certain areas remaining relatively inaccessible to the drug. Last, the retention of the drug in the tumor was far less than in normal tissues.
D000818:Animals; D001345:Autoradiography; D001932:Brain Neoplasms / Q000378:metabolism*; D004806:Ependymoma / Q000378:metabolism*; D005260:Female; D007275:Injections, Intravenous; D008727:Methotrexate / Q000008:administration & dosage / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000378:metabolism; D012983:Soft Tissue Neoplasms / Q000378:metabolism; D013997:Time Factors; D014316:Tritium
D014316:Tritium; D008727:Methotrexate