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In Vivo 31 P MRS Evaluation of Ganciclovir Toxicity in C6 Gliomas Stably Expressing the Herpes Simplex Thymidine Kinase Gene
Author(s) -
Stegman Lauren D.,
BenYoseph Oded,
Freyer James P.,
Ross Brian D.
Publication year - 1996
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/(sici)1099-1492(199612)9:8<364::aid-nbm436>3.0.co;2-w
Subject(s) - ganciclovir , thymidine kinase , herpes simplex virus , in vivo , suicide gene , growth inhibition , pharmacology , genetic enhancement , thymidine , toxicity , phosphocholine , microbiology and biotechnology , chemistry , biology , gene , medicine , cancer research , virology , virus , in vitro , biochemistry , human cytomegalovirus , genetics , phospholipid , membrane , phosphatidylcholine
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 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 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.