Detection of lentiviral suicide gene therapy in C6 rat glioma using hyperpolarised [1-13C]pyruvate

Riikka Nivajärvi, Venla Olsson, Viivi Hyppönen, Sean Bowen, Hanna M. Leinonen, Hanna P. Lesch, Jan Henrik Ardenkjær-Larsen, Olli H.J. Gröhn, Seppo Ylä-Herttuala, Mikko I. Kettunen*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Hyperpolarised [1-13C]pyruvate MRI has shown promise in monitoring therapeutic efficacy in a number of cancers including glioma. In this study, we assessed the pyruvate response to the lentiviral suicide gene therapy of herpes simplex virus-1 thymidine kinase with the prodrug ganciclovir (HSV-TK/GCV) in C6 rat glioma and compared it with traditional MR therapy markers. Female Wistar rats were inoculated with 106 C6 glioma cells. Treated animals received intratumoural lentiviral HSV-TK gene transfers on days 7 and 8 followed by 2-week GCV therapy starting on day 10. Animals were repeatedly imaged during therapy using volumetric MRI, diffusion and relaxation mapping, as well as metabolic [1-13C]pyruvate MRS imaging. Survival (measured as time before animals reached a humane endpoint and were euthanised) was assessed up to day 30 posttherapy. HSV-TK/GCV gene therapy lengthened the median survival time from 12 to 25 days. This was accompanied by an apparent tumour growth arrest, but no changes in diffusion or relaxation parameters in treated animals. The metabolic response was more evident in the case-by-case analysis than in the group-level analysis. Treated animals also showed a 37 ± 15% decrease (P < 0.05, n = 5) in lactate-to-pyruvate ratio between therapy weeks, whereas a 44 ± 18% increase (P < 0.05, n = 6) was observed in control animals. Hyperpolarised [1-13C]pyruvate MRI can offer complementary metabolic information to traditional MR methods to give a more comprehensive picture of the slowly developing gene therapy response. This may benefit the detection of the successful therapy response in patients.

Original languageEnglish
Article numbere4250
JournalNMR in Biomedicine
Volume33
Issue number4
Number of pages9
ISSN0952-3480
DOIs
Publication statusPublished - 1 Apr 2020

Keywords

  • Dissolution dynamic nuclear polarisation
  • Ganciclovir
  • Gene therapy
  • Glioma
  • Herpes simplex thymidine kinase
  • Metabolism
  • [1-C]pyruvate

Cite this

Nivajärvi, R., Olsson, V., Hyppönen, V., Bowen, S., Leinonen, H. M., Lesch, H. P., Ardenkjær-Larsen, J. H., Gröhn, O. H. J., Ylä-Herttuala, S., & Kettunen, M. I. (2020). Detection of lentiviral suicide gene therapy in C6 rat glioma using hyperpolarised [1-13C]pyruvate. NMR in Biomedicine, 33(4), [e4250]. https://doi.org/10.1002/nbm.4250