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Penetration of intra-arterially administered
vincristine in experimental brain tumor
Frances M. Boyle, Susan L. Eller, Stuart A. Grossman
Bill Walsh Cancer Research
Laboratories, Royal North Shore Hospital, Sydney, NSW 2065, Australia (F.M.B.);
Sidney Kimmel Cancer Center at Johns Hopkins Medical Center, Baltimore, MD
21231, USA (S.L.E., S.A.G.).
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 intraarterial
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
bloodbrain 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.
© 2003 Duke University Press
Source: http://lysander.ingentaselect.com/cgi-bin/linker?ini=dup_no&reqidx=/cw/dup/15228517/v6n4/s5/p300
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