Therapeutic efficacy of the thymidine kinase ganciclovir system on large experimental gliomas: a nuclear magnetic resonance imaging study

Contradictory experimental results and human trials have questioned the cli nical relevance of the HSVtk/ganciclovir system. To bypass the problem of t ransfection efficiency, we used a glioma cell line stably expressing the HS Vtk gene, which was also fully characterized from gene to protein. We also designed a more clinically relevant experimental protocol, consisting of la te GCV delivery on large tumor formations. In short-term studies, histologi cal examination revealed a significant decrease in tumor volume in GCV-trea ted animals from day 1 or from day 10 after cell inoculation. We observed t hat late GCV delivery is as efficient as early delivery, probably because G CV can reach tumor cells more easily when neoangiogenesis occurs. In long-t erm experiments, the survival of treated rats bearing 15-day tumors was imp roved by 60% compared with C6 control animals. Surprisingly, a 30% survival rate was observed in C6TK control animals. Nuclear magnetic resonance imag ing demonstrated, in all surviving animals, a complete regression of tumors without mass effect. These results clearly demonstrate that the HSVtk/GCV system remains a potent therapeutic strategy, even when tested in large tum ors, in contrast with the microscopic tumor formations previously reported.