In vivo 31P MRS evaluation of ganciclovir toxicity in C6 gliomas stably expressing the herpes simplex thymidine kinase gene.
Phosphorus MRS was evaluated as a monitor of tumour therapeutic response to the herpes simplex virus thymidine kinase suicide gene therapy paradigm. In vivo 31P spectra were obtained from subcutaneous rat C6 gliomas constitutively expressing the HSVtk gene post treatment with ganciclovir (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 31P 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 31P 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.
Stegman
L D
LD
Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor 48109, USA.
Ben-Yoseph
O
O
Freyer
J P
JP
Ross
B D
BD
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use* / Q000633:toxicity; D015774:Ganciclovir / Q000627:therapeutic use* / Q000633:toxicity; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D010758:Phosphorus; D051381:Rats; D011923:Rats, Nude; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics*; D013937:Thymidine Kinase / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D010758:Phosphorus; D013937:Thymidine Kinase; D015774:Ganciclovir