Effect of perfluorochemicals on BCNU chemotherapy in a 9L rat brain tumor model

Abstract

Perfluorochemicals are characterized by their small size and high propensity for carrying oxygen and carbon dioxide. This study was undertaken to identify the combined effect of a perfluorochemical (Fluosol-43, 20 ml/kg) and a chemotherapeutic agent (BCNU, LD10 dose: 13.3 mg/kg) in a 9L rat brain tumor model. Brain tumor was induced by intracerebral implantation of 9L rat glioma cells (7×105 cells) into male CD Fisher 344 rats weighing about 100 g. The tumor growth curve of this model was exponential, and at 7 days after implantation, the control animals had a macrotumor weighing about 51 mg. The tumor-bearing rats on day 7 after implantation were randomly divided into 5 groups: control; BCNU alone; Fluosol-43 with oxygen; Fluosol-43 plus BCNU; and Fluosol-43 plus BCNU with oxygen. High oxygen was produced in an oxygen chamber with 95% oxygen and 5% carbon dioxide, and the PaO2 was maintained between 300 and 400 mmHg. Control animals had a mean survival time of 15.23 ± 2.84 (S.D.) days, and the Fluosol-43 with oxygen group showed no prolongation of the mean survival time (p>0.2). BCNU treatment alone prolonged the mean survival time to 20.90 ± 3.80 days (p<0.05), whereas the Fluosol-43 plus BCNU group had no further prolongation of the mean survival time: The Fluosol-43 plus BCNU with oxygen showed a mean survival time of 32.27 ± 4.80 days, which was significantly longer than that of the BCNU treatment alone (p < 0.005). Perfluorochemicals (Fluosol-43) with oxygen may have a synergistic effect on BCNU chemotherapy for malignant brain tumor. Fluosol-43 with oxygen might have oxygenated the hypoxic cells so that they became sensitized to BCNU. Also, the transport of BCNU into hypoxic and hypovascular areas might have been enhanced by Fluosol-43 and oxygen.