A new MRI technique locates aggressive tumor cells

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Glioblastoma stem cells migrating from a tumor structure. Caroline Delmas
Glioblastoma stem cells migrating from a tumor structure. Caroline Delmas

Glioblastomas are highly aggressive brain tumors whose treatment consists of surgery and radiochemotherapy. A new medical imaging technique could improve patients’ prognosis, according to a recent clinical trial led by Élisabeth Moyal, Professor at Toulouse III - Paul Sabatier University and Head of the Radiotherapy Department at the IUCT-Oncopole. The results of her clinical trial conducted at Oncopole and within her Inserm research team at the Toulouse Cancer Research Center (CRCT - Inserm/CNRS/UT3), in collaboration with the neurosurgery department of Toulouse University Hospital, were published in the journal Science Advances on November 3.

Treatment of glioblastoma consists of surgical resection of the central tumor area (known as CE), followed by radiochemotherapy to the same area, as well as to the large peritumoral zone infiltrated by the tumor cells that have migrated there (known as the FLAIR zone). Despite this treatment, most patients will experience a relapse, particularly in those FLAIR peritumoral areas that were not removed during the initial surgery.

These are the high-risk areas studied by Prof. Elisabeth Moyal and her Inserm team. Indeed, using an MRI technique called magnetic resonance spectroscopy, which analyzes tumor metabolism, the team had previously shown that CE and FLAIR peritumoral tumor regions displaying hypermetabolism predicted where the tumor would recur after treatment.

Recurrences are mainly attributed to a more aggressive subpopulation of tumor cells, the glioblastoma stem cells. The researchers’ hypothesis was therefore that hypermetabolic regions were enriched in this population of cancer stem cells.

To verify this, a clinical trial was carried out on 16 patients with glioblastoma, who underwent preoperative conventional MRI combined with magnetic resonance spectroscopy, enabling biopsies to be taken during MRI-guided surgery in CE and FLAIR tumor areas, whether hypermetabolic or not. Patients were subsequently treated with standard radiochemotherapy.

Experiments carried out at the CRCT by Dr Anthony Lemarié, lecturer at UT3, and Caroline Delmas, laboratory engineer at the IUCT and CRCT, confirmed their hypothesis and demonstrated that hypermetabolic zones in FLAIR peritumoral regions were enriched in glioblastoma stem cells and overexpressed numerous genes involved in tumor aggressiveness and resistance. The greater the enrichment of glioblastoma stem cells in these hypermetabolic peritumoral areas, the more severe the prognosis for relapse.

" The combination of MRI imaging and magnetic resonance spectroscopy, prior to surgery, could enable better resection and therapeutic targeting of hypermetabolic zones present in peritumoral regions ," explains Prof. Elisabeth Moyal.

This specific targeting could improve the prognosis of these highly aggressive brain tumors.