Leukotriene E4 selectively increase the delivery of methotrexate to the C6 gliomas in rats.
Leukotriene E4 (LTE4) infused into the carotid artery ipsilateral to an experimental glial tumor will selectively increase the blood-tumor permeability within the tumor. In this study the effects of intracarotid infusion of LTE4 on blood-tumor barrier (BTB) permeability for intravenously administered 14C-aminoisobutyric acid, 14C-5-fluorouracil (5-FU) 14C-sucrose and 3H-methotrexate (MTX) were examined in C6 gliomas of rats. The intracarotic administration of LTE4 selectively opened the BTB, without affecting permeability of normal brain tissue, to all of the above tracers. Intracarotid infusion of LTE4 had the tendency to increase the uptake of intravenously administered 5-FU within the tumor, but this effect was not statistically significant. The intracarotid infusion of LTE4, however, increased the uptake of intravenously injected MTX about twofolds within the tumor (Ki = 19.48 +/- 1.06 vs 10.12 +/- 1.19, p < 0.01) without increasing the uptake in the normal brain tissue.
Chio
C C
CC
Department of Surgery (Division of Neurosurgery), National Cheng Kung University Medical Center, Tainan, Taiwan, R.O.C.
Lin
S J
SJ
Lin
M T
MT
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001345:Autoradiography; D001784:Blood Gas Analysis; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002339:Carotid Arteries; D005260:Female; D005472:Fluorouracil / Q000493:pharmacokinetics; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D007261:Infusions, Intra-Arterial; D017999:Leukotriene E4 / Q000008:administration & dosage / Q000494:pharmacology*; D008727:Methotrexate / Q000493:pharmacokinetics* / Q000627:therapeutic use; D009368:Neoplasm Transplantation; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D017999:Leukotriene E4; D005472:Fluorouracil; D008727:Methotrexate