New method for distinguishing tumour tissue could improve glioblastoma resection

Aggressive recurrent tumour

Glioblastoma (Glioblastoma multiforme) is the most common and also the most aggressive primary brain tumour. It originates from glial cells – astrocytes – and represents approximately 12–15% of all intracranial tumours. Its incidence is 2 to 3 new cases per 100,000 people annually. In the Czech Republic, approximately 350 new cases are diagnosed each year. Without properly targeted treatment, patient survival does not exceed three months.

Currently, glioblastoma can only be treated palliatively through radical surgical resection, aimed at reducing the pressure of the tumour on surrounding brain structures. Following surgery, adjuvant radiotherapy and chemotherapy are typically administered. Despite this, patients survive on average only one year after surgery. The median time to glioblastoma recurrence after standard therapy is approximately seven months. Fewer than 25% of patients survive beyond two years.

Due to the high recurrence rate of glioblastoma and the proximity of its resection to eloquent brain structures, maximum precision is critical for a successful procedure. At present, 5-aminolevulinic acid (5-ALA) is commonly used to determine the boundary between glioblastoma and healthy tissue. However, the fluorescent signal generated by 5-ALA often spreads beyond the tumour itself due to diffusion and also diminishes relatively quickly, resulting in imprecise resections.

More precise differentiation of tumour tissue using molecular probes

The research team therefore focused on a better way to distinguish tumour tissue from healthy brain tissue. The result is molecular probes designated as 6QC-ICQ, which contain a near-infrared (NIR) fluorophore, specifically indocyanine green (ICG). This fluorophore is activated by cysteine cathepsins in glioblastoma tumour cells and macrophages infiltrating the tumour. The resulting fluorophore accumulates intracellularly, allowing fluorescent visualisation of tumour tissue, while fluorescence in healthy br...

The 6QC-ICQ probes and other molecular probes were tested by researchers in mice with orthotopic brain tumours, in vitro in cell cultures, and ex vivo in biopsy material from patients with glioblastoma.

Subsequent confirmation using several visualisation platforms demonstrated that the 6QC-ICG probe can visualise tumour tissue significantly better than the currently used 5-ALA and other studied molecular probes. The study's conclusions were published in March in the Journal of Neurosurgery.

The authors of the research aim to transfer their findings into clinical practice as soon as possible. However, this requires optimisation of current imaging devices, which are typically configured for tumour detection using 5-ALA. Discussions with manufacturers of visualisation technologies and platforms are therefore underway, with the ultimate goal of developing an efficient tool based on the new 6QC-ICQ molecular probes.

Editorial Team, Medscope.pro

Sources:

1. Konečná D., Výmola P., Ternerová N. et al. Molecularly targeted protease-activated probes for visualization of glioblastoma: a comparison with 5-ALA. J Neurosurg 2024 Mar 29; 141 (3): 602–613, doi: 10.3171/2024.1.JNS231137.
2. Czech scientists' discovery lights up brain tumours for surgeons. National Institute for Cancer Research, 2024. Available from: www.nuvr.cz/2024/05/24/objev-ceskych-vedcu-chirurgum-rozsviti-mozkove-nadory