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Unterrainer, M.; Fleischmann, D. F.; Vettermann, F.; Ruf, V.; Kaiser, L.; Nelwan, D.; Lindner, S.; Brendel, M.; Wenter, V.; Stoecklein, S.; Herms, J.; Milenkovic, V. M.; Rupprecht, R.; Tonn, J. C.; Belka, Claus ORCID logoORCID: https://orcid.org/0000-0002-1287-7825; Bartenstein, Peter; Niyazi, Maximilian and Albert, Nathalie L. ORCID logoORCID: https://orcid.org/0000-0003-0953-7624 (2020): TSPO PET, tumour grading and molecular genetics in histologically verified glioma: a correlative F-18-GE-180 PET study. In: European Journal of Nuclear Medicine and Molecular Imaging, Vol. 47, No. 6: pp. 1368-1380

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Abstract

Background: The 18-kDa translocator protein (TSPO) is overexpressed in brain tumours and represents an interesting target for glioma imaging. F-18-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 F-18-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 F-18-GE-180 PET, and the maximal and mean tumour-to-Background: ratios (TBRmax, TBRmean) 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 F-18-GE-180-uptake was observed in all but 4 cases (being WHO grade II glioma, IDH-mutant). A high association of F-18-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 TBRmax 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 F-18-GE-180-uptake in IDH-wild-type gliomas in the overall group (median TBRmax 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 TBRmax 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 F-18-GE-180 PET are highly associated with the histological WHO grades, with the highest F-18-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 F-18-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.

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