The accumulation of the topoisomerase I inhibitor topotecan in brain tumor as well as in brain around tumor (BAT) and normal brain following an intravenous bolus of topotecan of 0.5 mg/kg was investigated in rats bearing a 9L glioma. Also the influence of dexamethasone (Dex) on the uptake of topotecan was examined. Tumor, BAT and brain tissue as well as whole blood were collected at 1 h after an i.v. bolus of topotecan. Concentrations of total topotecan in tumor, BAT and brain were quantified with high-performance liquid chromatography (HPLC) and compared with concentrations in plasma of total topotecan. In brain tumor tissue the mean total topotecan concentration was 96 ± 33 ng/g which was 20-fold higher than the accumulation of topotecan in normal brain tissue. In BAT intermediate concentrations of 13 ± 4.9 ng/g were reached. Mean total topotecan concentration in plasma was 100 ± 25 ng/ml. We did not find an influence of Dex on the uptake of topotecan in either tissue. We conclude that high tissue concentrations of topotecan can be reached in experimental brain tumors in rats. This observation may be useful in the design of clinical studies with topotecan.

Accumulation, Blood-brain barrier, Brain around tumor, Dexamethasone, Experimental brain tumor, Topotecan
dx.doi.org/10.1023/A:1006166716683, hdl.handle.net/1765/66031
Journal of Neuro-Oncology
Department of Neurology

Straathof, C.S.M, van den Bent, M.J, Loos, W.J, Vecht, C.J, & Schellens, J.H.M. (1999). The accumulation of topotecan in 9L glioma and in brain parenchyma with and without dexamethasone administration. Journal of Neuro-Oncology, 42(2), 117–122. doi:10.1023/A:1006166716683