An attempt to analyze the concentration of the chemotherapeutic agents in the extracellular fluid of the experimental brain tumor tissue using microdialysis technique

化疗药物在体内和体外的疗效有时是不同的。造成这种现象的一个重要因素可能是肿瘤组织中化疗药物的实际浓度。然而，化疗药物浓度的评估在技术上是困难的，而且没有建立方法。应用微透析技术成功地分析了脑肿瘤组织细胞外液中的药物浓度。本研究使用的化疗药物为ACNU和顺铂。细胞外液中药物的实际浓度（简称y）可从体外微透析通过以下演算获得的样品（简称x）的药物浓度计算出来。对于ACNU: y=8.36x-0.065，顺铂：y=8.43x+0.086，在9L大鼠胶质瘤中，药物浓度在20min达到最高值（5.41μg/ml），然后在静脉给药10mg ACNU时逐渐下降。顺铂2mg静脉给药10min时药物浓度最高（12.3μg/ml）。在转移性脑瘤（ACL15）中，ACNU 10mg给药20min时药物浓度最高（2.77μg/ml）。顺铂2mg给药10min时药物浓度最高（13.3μg/ml）。在两种肿瘤模型中，给药1mg ACNU和0.2mg顺铂时，药物浓度均低于检测水平。这些结果表明，当临床剂量的药物被系统使用时，脑肿瘤组织细胞外液中的药物浓度出乎意料地低。有必要尝试提高局部用药水平。

The efficacy of chemotherapeutic agents in vitro and in vivo sometimes divergent. One important factor responsible for this phenomenon is likely to be the actual concentration of the chemotherapeutic agent in the tumor tissue. However, the assessment of the concentration of the chemotherapeutic agents is technically difficult, and the methods are not established. We successfully analyzed the drug concentration in the extracellular fluid of the brain tumor tissue by use of microdialysis. The chemotherapeutic agents employed in this study were ACNU and cisplatinum. The actual concentration of the drug in the extracellular fluid (referred to y) is calculable from the drug concentration of the samples (referred to x) obtained by in vitro microdialysis via following calculus. For ACNU : y=8.36x-0.065, for cisplatinum : y=8.43x+0.086In the 9L rat glioma, the drug concentration showed highest value at 20min (5.41μg/ml) followed by a grudual decrease when 10mg of ACNU was administered intravenously. Whereas the drug concentration was highest at 10min (12.3μg/ml) when 2mg of cisplatinum was administered intravenously. In the metastatic brain tumor (ACL15), the drug concentration revealed highest value at 20min (2.77μg/ml) when 10mg of ACNU was administered. In contrast, the drug concentration was highest at 10min (13.3μg/ml) when 2mg of cisplatinum was administered. In the both tumor models, the drug concentration was below the detectable level when 1mg of ACNU and 0.2mg of cisplatinum were administered. These results suggest that the drug concentration in the extracellular fluid of the brain tumor tissue is unexpectedly low when a clinical dosis of the drug is used systemically. An attempt to raise the topical drug level is warranted.