In vivo 31 P MRS evaluation of ganciclovir toxicity in C6 gliomas stably expressing the herpes simplex thymidine kinase gene

Abstract

Phosphorus MRS was evaluated as a monitor of tumour therapeutic response to the herpes simplex virus thymidine kinase suicide gene therapy paradigm. In vivo 31 P spectra were obtained from subcutaneous rat C6 gliomas constitutively expressing the HSVtk gene post treatment with gancielovir (GCV, 15 mg/kg i.p., twice-daily). Significant regression ( p <0.1) of tumour volume was observed 10 days after beginning GCV administration. However, no changes in tumour pH or energy metabolites from pre-treatment values were observed. High-resolution 31 P spectra of tumour extracts revealed a statistically significant reduction in the phosphocholine to phosphoethanolamine ratio six days post-GCV administration. These results indicate that the HSVtk/GCV-induced killing of tumours is not associated with corresponding changes in 31 P MRS-observable energy metabolites and pH. The observed reduction in the PE/PC ratio may provide a non-invasive in vivo indicator of therapeutic efficacy. © 1996 by John Wiley & Sons, Ltd.