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

Abstract

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 (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 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 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 18F-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 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.

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Acknowledgements

We thank Prof. Dr. C. Wetzel for the support regarding polymorphism genotyping. Additionally, we thank Joanne Stevens and GE Healthcare for the support regarding tracer production. N. Albert gratefully acknowledges the Else Kröner-Fresenius-Stiftung for the financial support of her research.

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Correspondence to N. L. Albert.

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Conflict of interest

N.L.A. is a member of the Neuroimaging Committee of the EANM. P.B. has received a speaker honorarium from GE Healthcare. All other authors declare that they have no conflicts of interest.

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The study was authorized by the local ethics committee (IRB 17-769) in accordance with the ICH Guideline for Good Clinical Practice (GCP) and the Declaration of Helsinki.

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All patients gave written consent to undergo PET scans.

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Unterrainer, M., Fleischmann, D.F., Vettermann, F. et al. TSPO PET, tumour grading and molecular genetics in histologically verified glioma: a correlative 18F-GE-180 PET study. Eur J Nucl Med Mol Imaging 47, 1368–1380 (2020). https://doi.org/10.1007/s00259-019-04491-5

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Keywords

  • 18F-GE-180
  • TSPO
  • Glioma
  • Grading
  • Molecular genetics