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

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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.