脳腫瘍治療におけるperfluorochemicalsと放射線照射併用療法の基礎的研究

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Perfluorochemicals (Fluoso1-43) are characterized by their small size and high propensity for car-rying oxygen and carbon dioxide, and also have the ability of improving the cerebral microcircula-tion. This study was undertaken to identify the combined effect of perfluorochemicals and irradia-tion in a rat brain tumor model. Brain tumors were induced by intracerebral implantation of 9L rat glioma cells (7X10^5 cells) into male CD Fisher 344 rats, weighing about 100 g. To test the possibility of enhancing superoxide radical (O_2) toxicity by Fluosol-43 treatment, tumor-bearing rats were treated with the drug diethyldithiocarbamate (DDC), an inhibitor of superoxide dismutase (SOD) which eliminates theO_2 radical in cells. After 1 hour of intraperito-neal infusion of 1 g/kg DDC, the SOD activity in the brain and brain tumor decreased to 48% and 79% of that of the controls respectively. The tumor-bearing rats were randomly divided into 4 groups; control, DDC alone, DDC with oxygen, and DDC plus Fluosol-43 with oxygen. The tumors of the control animals had a mean colony forming efficiency of 18.3±5.8 (SD)%. The mean colony forming efficiency of DDC alone, DDC with oxygen, and DDC plus Fluosol-43 with oxygen treated tumors was 13.4±4.2%, 10.5±4.9%, and 5.2±4.3% recpectively. Tumor-bearing rats were randomly divided into 6 groups; control, Fluosol-43 with oxygen, radiation alone (1,500 rads), radiation with oxygen, Fluosol-43 plus radiation, and Fluosol-43 plus radiation with oxygen. The control animals has a mean survival time of 14.2±1.3 (SD) days and the Fluosol-43 with oxy-gen group showed no prolongation of the mean survival time. The radiation alone, radiation with oxygen, and Fluosol-43 plus radiation groups prolonged the mean survival time to 16.1±2.3 days, 15.6±1.6 days, and 15.5±2.3 days respectively (P<0.01) . The Fluosol-43 plus radiation with oxy-gen group showed a mean survival time of 19.8±2.4 days, which was significantly longer than that of the radiation with oxygen group (P<0.01). Perfluorochemicals (Fluosol-43) with oxygen may have a synergistic effect on the radiation therapy for malignant brain tumor. Fluosol-43 with oxygen might have oxygenated the hypoxic cells to make them sensitized to radiation.
日本脳神経外科学会の論文
1984-04-15

脳腫瘍治療におけるperfluorochemicalsと放射線照射併用療法の基礎的研究

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