Tumor and tissue distribution of a methotrexate-anti-EL4 immunoglobulin conjugate in EL4 lymphoma-bearing mice.
The uptake and tissue distribution of [3H]methotrexate [( 3H]MTX) at doses of 5 mg/kg i.p. either free or linked to anti-EL4 immunoglobulin G (AELG) or normal rabbit globulin (NRG) was studied in EL4 lymphoma-bearing C57BL/6J mice. When the uptakes of MTX-AELG, MTX-NRG, and free MTX were assayed as cell-associated 3H activity, comparison 3 hr after administration showed that uptake of MTX administered as the AELG conjugate was 2.5 times the uptake of MTX administered as the NRG conjugate and 6 times the uptake of MTX administered free. In contrast to the difference in the uptake of MTX-AELG and MTX-NRG by tumor cells, the pattern of uptake in all the other tissues studied was generally similar for the two conjugates. Conjugated MTX persisted in all tissues and serum and ascites fluid, whereas free MTX declined rapidly after reaching peak levels around 1 hr, except in EL4 cells where 45% was retained at 24 hr. The levels of intracellular MTX after administration of these three agents exceeded the intracellular dihydrofolate reductase level and correlated with the relative tumor-inhibitory effect in vivo of the agent (MTX-AELG greater than MTX-NRG greater than MTX).
D000818:Animals; D000936:Antigen-Antibody Complex / Q000032:analysis; D001692:Biological Transport; D002460:Cell Line; D005260:Female; D007074:Immunoglobulin G / Q000378:metabolism*; D007700:Kinetics; D008223:Lymphoma / Q000276:immunology*; D008727:Methotrexate / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D014018:Tissue Distribution; D014316:Tritium
D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D014316:Tritium; D008727:Methotrexate