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Delivery of a novel nitrosourea, MCNU, to the brain tissue in glioma-bearing rats

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Summary

We observed the tissue delivery of a novel water-soluble nitrosourea, 1-(2-chloroethyl)-3-(methyl-α-D-glucopyranos-6-yl)-1-nitrosourea (MCNU) in rats bearing experimental brain tumors by conducting autoradiography on all. Prior to this study, the development of a streaming phenomenon was ascertained (and thus finding the optimum velocity for intra-arterial infusion) by14C-iodoantipyrine (IAP) autoradiography. Furthermore, a single pass extraction value of MCNU was measured. At an arterial infusion rate of 0.2 ml/min., the streaming phenomenon was recognized but the tracer was fairly evenly distributed at a rate of 1.0 ml/min. On the other hand, the single pass extraction value for MCNU was 0.18 ± 0.036 (mean ±S.D., n=3, under pentobarbital anesthesia). It was suggested that MCNU is very unlikely to be transported into the normal rat brain. We conducted14C-MCNU autoradiography to observe tissue distribution of MCNU following its intra-arterial and intravenous infusions in a brain tumor model using rats. The normal side (the side where no infusions were given) and the cerebral cortex at the side affected by the tumor (the side where the infusion was given) showed hardly any uptake of14C-MCNU in both the intra-arterial and intravenous infusion groups. The tumorous section was divided into the periphery and the center to measure tissue concentration of the tracer in each section. Compared against the cortical section, the periphery and the center showed significant increases in the concentration (approximately 11 to 15 times and 3 to 7 times, respectively, the figure for the cortical region) for both the intra-arterial and intravenous groups. When compared against the intravenous infusion group, the arterial infusion group showed a significantly high rate of accumulation (1.3 to 3.9 times).

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Authors and Affiliations

  1. Department of Neurosurgery, Asahikawa Medical College, 4-5-3 Nishikagura, Asahikawa, Hokkaido 078, Japan

    Akira Hodozuka, Kazuhiro Sako, Hirofumi Nakai, Masayuki Tomabechi, Nozomi Suzuki & Yukichi Yonemasu

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  1. Akira Hodozuka
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  2. Kazuhiro Sako
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  3. Hirofumi Nakai
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  4. Masayuki Tomabechi
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  5. Nozomi Suzuki
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  6. Yukichi Yonemasu
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Hodozuka, A., Sako, K., Nakai, H. et al. Delivery of a novel nitrosourea, MCNU, to the brain tissue in glioma-bearing rats. J Neuro-Oncol 15, 79–86 (1993). https://doi.org/10.1007/BF01050267

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