Kokunai T, Kuwamura K
No To Shinkei. 1982 Jun;34(6):609-15.
Perfluorochemicals (Fluosol-43) is characterized with its small size and high propensity for carrying oxygen and carbon dioxide, and also have the function to improve the cerebral microcirculation. These characteristic features of Fluosol-43 may have a beneficial effect on brain-tumor chemotherapy in terms of the oxygenation of hypoxic cells, and/or the improvement of the pharmacokinetics of anticancer drugs. This study was undertaken to identify the combined effect of perfluorochemicals (Fluosol-43, 20 ml/kg) and chemotherapeutic agent (BCNU, LD10 dose; 13.3 mg/kg) in a rat brain-tumor model. Brain-tumor model was made by the intracerebral implantation of C6 rat glioma cells (1 X 10(5) cells/10 microliters). At 10 days after implantation, control animals had a macrotumor weighing about 100 mg with large part of central necrosis. The tumor-bearing rats for 10 days after implantation were randomly divided into 4 groups; a control group, a Fluosol-43 treatment group, a BCNU treatment group, and a Fluosol-43 plus BCNU treatment group. Control animals had mean survival time of 19.94 +/- 2.41 (S.D.) days, and mean survival time of Fluosol-43 treatment group was 19.47 +/- 1.36 days. BCNU treatment alone prolonged the mean survival time to 28.36 +/- 7.94 days (p less than 0.001). Fluosol-43 plus BCNU treatment group showed 36.00 +/- 10.15 days, which was significantly greater than that of BCNU treatment alone group (p less than 0.005). The long survivals lived over 50 days after implantation were 7 out of 27 rats in Fluosol-43 plus BCNU treatment group, in contrast to one out of 25 rats in BCNU treatment alone group. Perfluorochemicals (Fluosol-43) may have the synergistic effect on BCNU chemotherapy for brain tumors. It was speculated for the above results that following the oxygenation of hypoxic cells by Fluosol-43, hypoxic cells might be sensitized to BCNU, which might be much delivered into hypoxic area. And further studies should be done for the evaluation of the mechanism of perfluorochemicals on brain tumor experimentally before clinical application.
全氟化合物（氟碳乳剂-43）的特点是颗粒小，携带氧气和二氧化碳的能力强，还具有改善脑微循环的功能。氟碳乳剂-43的这些特性可能在缺氧细胞的氧合作用和/或抗癌药物药代动力学的改善方面对脑肿瘤化疗产生有益影响。本研究旨在确定全氟化合物（氟碳乳剂-43，20毫升/千克）与化疗药物（卡氮芥，半数致死剂量；13.3毫克/千克）在大鼠脑肿瘤模型中的联合作用。通过脑内植入C6大鼠胶质瘤细胞（1×10⁵细胞/10微升）建立脑肿瘤模型。植入后10天，对照动物有一个重约100毫克的大肿瘤，大部分为中央坏死。植入后10天的荷瘤大鼠随机分为4组；对照组、氟碳乳剂-43治疗组、卡氮芥治疗组和氟碳乳剂-43加卡氮芥治疗组。对照动物的平均生存时间为19.94±2.41（标准差）天，氟碳乳剂-43治疗组的平均生存时间为19.47±1.36天。单独使用卡氮芥治疗可将平均生存时间延长至28.36±7.94天（p＜0.001）。氟碳乳剂-43加卡氮芥治疗组的平均生存时间为36.00±10.15天，显著长于单独使用卡氮芥治疗组（p＜0.005）。氟碳乳剂-43加卡氮芥治疗组27只大鼠中有7只在植入后存活超过50天，而单独使用卡氮芥治疗组25只大鼠中只有1只。全氟化合物（氟碳乳剂-43）可能对卡氮芥治疗脑肿瘤有协同作用。根据上述结果推测，氟碳乳剂-43使缺氧细胞氧合后，缺氧细胞可能对卡氮芥敏感，且卡氮芥可能更多地输送到缺氧区域。在临床应用前，应进一步开展实验研究以评估全氟化合物对脑肿瘤的作用机制。
