Control of solid tumor metastases with a high-molecular-weight derivative of methotrexate.
Methotrexate (MTX) covalently bound to bovine serum albumin (MTX-BSA), injected ip (10 mg/kg) once every 4 days for a total of 4 doses, was more effective than an equivalent dose of free MTX in reducing the number of metastases observed in female (C57BL/6 X DBA/2)F1 mice bearing the sc implanted Lewis lung carcinoma. Treatment with the high-molecular-weight derivative of MTX in addition caused a decreased rate of growth of the primary tumor and a modest increase in the life-span of the tumor-bearing animal. When tumor-bearing mice were killed after receiving injections of [3H]MTX or [3H]MTX-BSA, no difference in the amount of drug was found at the tumor site after 1 hour; however, after 8 or 24 hours, twice as much radioactivity was found in the tumors of mice treated with carrier-bound drug. Analysis of this radioactivity indicated a ratio of 60--80% carrier-bound to 20--40% free MTX.
D000818:Animals; D005260:Female; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008727:Methotrexate / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D008970:Molecular Weight; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D009374:Neoplasms, Experimental / Q000188:drug therapy; D012710:Serum Albumin, Bovine / Q000008:administration & dosage
D012710:Serum Albumin, Bovine; D008727:Methotrexate