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Towards a better detection of glioblastoma infiltration


Glioblastoma is a very aggressive cancer of the central nervous system, mainly because of its ability to infiltrate the surrounding areas. A collaboration led by a team of SHFJ (CEA-Joliot) and involving NeuroSpin (CEA-Joliot) demonstrates the interest of two imaging techniques for the early detection of tumor infiltration.

Results were published in Neuro-Oncology

Published on 26 February 2019

Abstract from the original paper :

Background

Glioblastoma (GBM) is the most devastating brain tumor. Despite the use of multimodal treatments, most patients relapse, often due to the highly invasive nature of gliomas. However, the detection of glioma infiltration remains challenging. The aim of this study was to assess advanced PET and MRI techniques for visualizing biological activity and infiltration of the tumor.

Methods

Using multimodality imaging, we investigated [18F]DPA-714, a radiotracer targeting the 18 kDa translocator protein (TSPO), [18F]FET PET, non-Gaussian diffusion MRI (apparent diffusion coefficient, kurtosis), and the S-index, a composite diffusion metric, to detect tumor infiltration in a human invasive glioma model. In vivo imaging findings were confirmed by autoradiography and immunofluorescence.

Results

Increased tumor-to-contralateral [18F]DPA-714 uptake ratios (1.49 ± 0.11) were found starting 7 weeks after glioma cell implantation. TSPO-PET allowed visualization of glioma infiltration into the contralateral hemisphere 2 weeks earlier compared with the clinically relevant biomarker for biological glioma activity [18F]FET. Diffusion-weighted imaging (DWI), in particular kurtosis, was more sensitive than standard T2-weighted MRI to detect differences between the glioma-bearing and the contralateral hemisphere at 5 weeks. Immunofluorescence data reflect in vivo findings. Interestingly, labeling for tumoral and stromal TSPO indicates a predominant expression of TSPO by tumor cells.

Conclusion

These results suggest that advanced PET and MRI methods, such as [18F]DPA-714 and DWI, may be superior to standard imaging methods to visualize glioma growth and infiltration at an early stage.


​PET images after injection of [18F]DPA-714 radiotracer, 1, 3, 5, 7 and 9 weeks after glioblastoma cells implantation in the striatum of a rodent model. The white lines delimit the cranial box. Three areas are delimited by white circles: an area around the tumor cell injection point (right), the equivalent area in the other hemisphere (middle), and the corpus callosum (left). These images indicate that the tumor grows over time and infiltrates the other cerebral hemisphere.
© Pigeon et al. Oxford University Press


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