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Imaging telomerase reverse transcriptase expression in oligodendrogliomas using hyperpolarized
Georgios Batsios1, Celine Taglang1, Anne Marie Gillespie1
1Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, USA.
Neuro-Oncology Advances
|August 21, 2023
Summary
Hyperpolarized 13C imaging with δ-[1-13C]-gluconolactone can monitor telomerase reverse transcriptase (TERT) expression and treatment response in oligodendrogliomas. This novel imaging agent detects early therapeutic effects before MRI changes occur.
Area of Science:
- Oncology
- Molecular Imaging
- Metabolic Imaging
Background:
- Telomere maintenance via telomerase reverse transcriptase (TERT) is crucial for cancer cell immortality, particularly in oligodendrogliomas.
- TERT expression in oligodendrogliomas correlates with increased glucose-6-phosphate dehydrogenase (G6PD) activity, a key enzyme in the pentose phosphate pathway (PPP).
- Hyperpolarized 13C imaging of δ-[1-13C]-gluconolactone metabolism to 6-phosphogluconate (6-PG) has shown potential for probing the PPP in brain tumors.
Purpose of the Study:
- To evaluate the utility of hyperpolarized 13C imaging using δ-[1-13C]-gluconolactone for monitoring TERT expression in oligodendrogliomas.
- To assess the ability of this imaging technique to track the response to telomere uncapping agents like 6-thio-2'-deoxyguanosine (6-thio-dG).
Main Methods:
- Patient-derived oligodendroglioma cells and orthotopic tumor models in rats were used to investigate the TERT-δ-[1-13C]-gluconolactone metabolism link.
- In vivo imaging studies were conducted to assess the correlation between TERT status, response to 6-thio-dG, and hyperpolarized 13C imaging signals.
- TERT expression was manipulated using doxycycline-inducible silencing and rescue systems to observe effects on G6PD activity and 6-PG production.
Main Results:
- Silencing TERT in oligodendroglioma cells led to decreased 6-PG production, confirming the dependence on TERT-driven G6PD activity.
- Restoring TERT expression reversed this effect, highlighting the dynamic relationship between TERT and PPP metabolism.
- In vivo imaging successfully differentiated TERT-expressing tumors from normal brain tissue based on 6-PG production and detected early therapeutic effects of 6-thio-dG prior to MRI-detectable changes.
Conclusions:
- Hyperpolarized δ-[1-13C]-gluconolactone imaging serves as a sensitive reporter of TERT expression in oligodendrogliomas.
- This imaging modality can monitor early responses to therapies targeting telomere maintenance, such as 6-thio-dG.
- The findings introduce a novel imaging agent for assessing tumor proliferation and treatment efficacy in oligodendroglioma patients.
