Detection of lentiviral suicide gene therapy in C6 rat glioma using hyperpolarised [1-13 C]pyruvate.
Riikka NivajärviVenla OlssonViivi HyppönenSean BowenHanna M LeinonenHanna P LeschJan Henrik Ardenkjaer-LarsenOlli H J GröhnSeppo Ylä-HerttualaMikko I KettunenPublished in: NMR in biomedicine (2020)
Hyperpolarised [1-13 C]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 [1-13 C]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 [1-13 C]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.
Keyphrases
- data analysis
- gene therapy
- herpes simplex virus
- contrast enhanced
- magnetic resonance imaging
- high resolution
- newly diagnosed
- randomized controlled trial
- healthcare
- end stage renal disease
- ejection fraction
- diffusion weighted imaging
- cell proliferation
- clinical trial
- cell cycle
- gene expression
- mass spectrometry
- peritoneal dialysis
- transcription factor
- prognostic factors
- tyrosine kinase
- bone marrow
- high density
- young adults
- drug release