TSPO PET, tumour grading and molecular genetics in histologically verified glioma: a correlative ¹⁸F-GE-180 PET study

Background: The 18-kDa translocator protein (TSPO) is overexpressed in brain tumours and represents an interesting target for glioma imaging. ¹⁸F-GE-180, a novel TSPO ligand, has shown improved binding affinity and a high target-to-background contrast in patients with glioblastoma. However, the association of uptake characteristics on TSPO PET using ¹⁸F-GE-180 with the histological WHO grade and molecular genetic features so far remains unknown and was evaluated in the current study.

Methods: Fifty-eight patients with histologically validated glioma at initial diagnosis or recurrence were included. All patients underwent ¹⁸F-GE-180 PET, and the maximal and mean tumour-to-background ratios (TBR_max, TBR_mean) as well as the PET volume were assessed. On MRI, presence/absence of contrast enhancement was evaluated. Imaging characteristics were correlated with neuropathological parameters (i.e. WHO grade, isocitrate dehydrogenase (IDH) mutation, O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and telomerase reverse transcriptase (TERT) promoter mutation).

Results: Six of 58 patients presented with WHO grade II, 16/58 grade III and 36/58 grade IV gliomas. An (IDH) mutation was found in 19/58 cases, and 39/58 were classified as IDH-wild type. High ¹⁸F-GE-180-uptake was observed in all but 4 cases (being WHO grade II glioma, IDH-mutant). A high association of ¹⁸F-GE-180-uptake and WHO grades was seen: WHO grade IV gliomas showed the highest uptake intensity compared with grades III and II gliomas (median TBR_max 5.15 (2.59-8.95) vs. 3.63 (1.85-7.64) vs. 1.63 (1.50-3.43), p < 0.001); this association with WHO grades persisted within the IDH-wild-type and IDH-mutant subgroup analyses (p < 0.05). Uptake intensity was also associated with the IDH mutational status with a trend towards higher ¹⁸F-GE-180-uptake in IDH-wild-type gliomas in the overall group (median TBR_max 4.67 (1.56-8.95) vs. 3.60 (1.50-7.64), p = 0.083); however, within each WHO grade, no differences were found (e.g. median TBR_max in WHO grade III glioma 4.05 (1.85-5.39) vs. 3.36 (2.32-7.64), p = 1.000). No association was found between uptake intensity and MGMT or TERT (p > 0.05 each).

Conclusion: Uptake characteristics on ¹⁸F-GE-180 PET are highly associated with the histological WHO grades, with the highest ¹⁸F-GE-180 uptake in WHO grade IV glioblastomas and a PET-positive rate of 100% among the investigated high-grade gliomas. Conversely, all TSPO-negative cases were WHO grade II gliomas. The observed association of ¹⁸F-GE-180 uptake and the IDH mutational status seems to be related to the high inter-correlation of the IDH mutational status and the WHO grades.