Penetration of intra-arterially administered vincristine in experimental brain tumor

Frances M. Boyle, Susan L. Eller, Stuart A Grossman

Research output: Contribution to journalArticle

Abstract

Vincristine is an integral part of the "PCV" regimen that is commonly administered to treat primary brain tumors. The efficacy of vincristine as a single agent in these tumors has been poorly studied. This study was designed to determine whether vincristine enters normal rat brain or an intracranially or subcutaneously implanted glioma and to assess the presence of the efflux pump P-glycoprotein (P-gp) on tumor and vascular endothelial cells. The 9L rat gliosarcoma was implanted intracranially and subcutaneously in three Fischer 344 rats. On day 7, [3H]vincristine (50 μCi, 4.8 μg) was injected into the carotid artery, and the animals were euthanized 10 or 20 min later. Quantitative autoradiography revealed that vincristine levels in the liver were 6- to 11-fold greater than in the i.c. tumor, and 15- to 37-fold greater than in normal brain, the reverse of the expected pattern with intra-arterial delivery. Vincristine levels in the s.c. tumor were 2-fold higher than levels in the i.c. tumor. P-gp was detected with JSB1 antibody in vascular endothelium of both normal brain and the i.c. tumor, but not in the tumor cells in either location, or in endothelial cells in the s.c. tumor. These results demonstrate that vincristine has negligible penetration of normal rat brain or i.c. 9L glioma despite intra-arterial delivery and the presence of blood-brain barrier dysfunction as demonstrated by Evan's blue. Furthermore, this study suggests that P-gp-mediated efflux from endothelium may explain these findings. The lack of penetration of vincristine into brain tumor and the paucity of single-agent activity studies suggest that vincristine should not be used in the treatment of primary brain tumors.

Original languageEnglish (US)
Pages (from-to)300-305
Number of pages6
JournalNeuro-Oncology
Volume6
Issue number4
DOIs
StatePublished - Oct 2004

Fingerprint

Vincristine
Brain Neoplasms
P-Glycoprotein
Neoplasms
Glioma
Brain
Endothelial Cells
Gliosarcoma
Evans Blue
Inbred F344 Rats
Vascular Endothelium
Blood-Brain Barrier
Autoradiography
Carotid Arteries
Endothelium
Antibodies
Liver

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Clinical Neurology

Cite this

Penetration of intra-arterially administered vincristine in experimental brain tumor. / Boyle, Frances M.; Eller, Susan L.; Grossman, Stuart A.

In: Neuro-Oncology, Vol. 6, No. 4, 10.2004, p. 300-305.

Research output: Contribution to journalArticle

Boyle, Frances M. ; Eller, Susan L. ; Grossman, Stuart A. / Penetration of intra-arterially administered vincristine in experimental brain tumor. In: Neuro-Oncology. 2004 ; Vol. 6, No. 4. pp. 300-305.
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