Summary

The 18 kDa translocator protein (TSPO) is expressed both within glioblastoma and in its immediate microenvironment. However, TSPO upregulation may also reflect systemic immune responses. To investigate this, total-body PET imaging was performed on glioblastoma-bearing mice at early (days 5–13) and late (days 18–19) stages, alongside a control (sham-inoculated) group, to analyze organ-organ interactions. The primary radiotracer, [¹⁸F]GE-180, was cross-validated using [¹⁸F]DPA-714.

Results from nanoScan® PET/CT 

Mice (n = 67) divided into three experimental groups received [¹⁸F]GE-180 (12.6 ± 3.3 MBq) and were scanned in the 40-60 post-injection window using a nanoScan™ S122P PET/CT scanner. For cross-validation, [¹⁸F]DPA-714 PET scans (15.83 ± 3.84 MBq, n = 71) were also acquired. To track tumor progression, mice underwent one to three scans. CT imaging was performed for anatomical coregistration and material density mapping.PET raw data were binned into 28 dynamic frames and reconstructed using the Tera-Tomo 3D algorithm (4 iterations, 12 subsets, 0.4 mm³ isotropic voxel size). Reconstructed CT images had an isotropic voxel size of 0.23 mm³.

Fig. 1 Mean [¹⁸F]GE-180 uptake ratios of various volumes of interest (VOIs). a Fused average PET and CT scans of late-stage (GBM late) and early-stage (GBM early) glioblastoma-bearing mice and sham-injected mice (sham), showing the tumor region, cerebellum, and contralateral hemisphere outlined in white, black, and grey, respectively (top). Bottom left, the 3D-rendered skeleton of a late-stage glioblastoma-bearing mouse with VOIs in red (heart), blue (lungs), and pink (bones); bottom right, the corresponding fused TSPO-PET scan with the heart and lungs outlined in black and white, respectively. Mean uptake ratios in the b tumor region, cerebellum, and contralateral hemisphere, c bones, and d heart and lungs of late-stage and early-stage glioblastoma-bearing mice and sham-injected mice.

Cross-validating [¹⁸F]GE-180 against [¹⁸F]DPA-714 proved challenging due to variations in injected cell numbers, survival times, and scan schedules. Nevertheless, the findings demonstrated stage-dependent changes in inter-organ TSPO connectivity, highlighting systemic effects that should be considered during diagnosis and treatment planning.

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