TSPO-PET and diffusion-weighted MRI for imaging a mouse model of infiltrative human glioma.

Background: Glioblastoma 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 positron emission tomography (PET) and magnetic resonance imaging (MRI) techniques for visualizing biological activity and infiltration of the tumor.

Methods: Using multi-modality imaging, we investigated [18F]DPA-714, a radiotracer targeting the 18kDa translocator protein (TSPO), [18F]FET PET, non-Gaussian diffusion MRI (ADC0, Kurtosis), and the S-index, a composite diffusion metric, to detect tumor infiltration in a human invasive glioma model. Invivo 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 two weeks earlier compared to the clinically relevant biomarker for biological glioma activity [18F]FET. Diffusion-weighted MRI (DWI), in particular kurtosis was more sensitive than standard T2w MRI to detect differences between the glioma-bearing and the contralateral hemisphere at 5 weeks. Immunofluorescence data reflect invivo findings. Interestingly, labelling for tumoral and stromal TSPO indicates a predominant expression of TSPO by tumor cells.

Conclusion: These results suggest that advanced PET and MR imaging 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.