THE VASCULAR COMPARTMENT HAMPERS ACCURATE DETERMINATION OF TENIPOSIDEPENETRATION INTO BRAIN-TUMOR TISSUE

After a pre-operative l-h i.v infusion of 150 mg/m(2) of teniposide (V umon; VM26), the drug levels were determined in resected brain tumor s pecimens from three patients with malignant glioma and from three pati ents with brain metastases. Tissue dissections were performed within 0 -2.5 h after drug administration in three patients and after 24 h in t he other three patients. Teniposide was quantified by high-performance liquid chromatography and the levels of albumin in the resected tissu e samples were quantified by radial immunodiffusion. In addition, albu min levels were quantified in normal brain tissue, in malignant glioma and in metastatic brain tumor tissue obtained post mortem from deceas ed patients. The albumin levels indicated that a substantial fraction (range: 0.16-0.50) of the resected brain tumor specimens consisted of blood. As the plasma concentration of teniposide during the first hour s after infusion is high, the major part of the drug measured in the t umor specimens collected within 2.5 h after drug administration origin ated from the blood compartment. At 24 h after drug administration, wh en the plasma level of teniposide had declined to approximately 0.20 m u g/ml, we could discern a real tissue uptake of teniposide ranging fr om 0.15-0.27 mu/g wet tissue weight in the resected tumor. Although th e number of patients in this study is small, this work clearly illustr ates that an accurate determination of the tissue concentration of ten iposide is hindered by the high concurrent plasma levels. It is theref ore essential that future tissue distribution studies also include a s uitable procedure that establishes the contribution of drug originatin g from the blood compartment.