GANCICLOVIR MEDIATED REGRESSION OF RAT-BRAIN TUMORS EXPRESSING THE HERPES-SIMPLEX VIRUS THYMIDINE KINASE IMAGED BY MAGNETIC-RESONANCE

Using a rat C6 brain tumor model, we studied the antitumor effects of Herpes simplex virus type 1 thymidine kinase (HSV-tk) gene transfer fo llowed by ganciclovir treatment. C6 glioma cells were transfected in v itro with the HSV-tk gene, and tested for their sensitivity to gancicl ovir. Although there was no surviving cell at a 30 mu M ganciclovir co ncentration, unmodified C6 cells were not affected by the drug. For in vivo experiments, intracerebral tumors were induced in rats by stereo tactic injection of 10(4) HSV-tk-modified C6 cells. Ten days later, th e animals were treated with intraperitoneal injections of ganciclovir for 21 days. The tumors evolution was evaluated by high resolution mag netic resonance imaging. In 33% of the rats, the signal intensity of t he tumors became heterogeneous, with development of highly hyperintens e areas, and a complete tumor regression was subsequently noted. Histo logical examination of successfully treated tumors revealed progressiv e necrosis with formation of cysts. The survival time of the HSV-tk/ga nciclovir treated animals was consistently increased, all rats survivi ng more than 30 days and 33% of them being still alive after 80 days.