Comparison of 18F-GE-180 and dynamic 18F-FET PET in high grade glioma: a double-tracer pilot study
PET represents a valuable tool for glioma imaging. In addition to amino acid tracers such as 18F-FET, PET targeting the 18-kDa mitochondrial translocator-protein (TSPO) is of high interest for high-grade glioma (HGG) imaging due to its upregulation in HGG cells. 18F-GE-180, a novel TSPO ligand, has shown a high target-to-background contrast in HGG. Therefore, we intra-individually compared its uptake characteristics to dynamic 18F-FET PET and contrast-enhanced MRI in patients with HGG.
Twenty HGG patients (nine IDH-wildtype, 11 IDH-mutant) at initial diagnosis (n = 8) or recurrence (n = 12) were consecutively included and underwent 18F-GE-180 PET, dynamic 18F-FET PET, and MRI. The maximal tumour-to-background ratios (TBRmax) and biological tumour volumes (BTV) were evaluated in 18F-GE-180 and 18F-FET PET. Dynamic 18F-FET PET analysis included the evaluation of minimal time-to-peak (TTPmin). In MRI, the volume of contrast-enhancement was delineated (VOLCE). Volumes were spatially correlated using the Sørensen–Dice coefficient.
The median TBRmax tended to be higher in 18F-GE-180 PET compared to 18F-FET PET [4.58 (2.33–8.95) vs 3.89 (1.56–7.15); p = 0.062] in the overall group. In subgroup analyses, IDH-wildtype gliomas showed a significantly higher median TBRmax in 18F-GE-180 PET compared to 18F-FET PET [5.45 (2.56–8.95) vs 4.06 (1.56–4.48); p = 0.008]; by contrast, no significant difference was observed in IDH-mutant gliomas [3.97 (2.33–6.81) vs 3.79 (2.01–7.15) p = 1.000]. Only 5/20 cases showed higher TBRmax in 18F-FET PET compared to 18F-GE-180 PET, all of them being IDH-mutant gliomas. No parameter in 18F-GE-180 PET correlated with TTPmin (p > 0.05 each). There was a tendency towards higher median BTVGE-180 [32.1 (0.4–236.0) ml] compared to BTVFET [19.3 (0.7–150.2) ml; p = 0.062] with a moderate spatial overlap [median Sørensen–Dice coefficient 0.55 (0.07–0.85)]. In MRI, median VOLCE [9.7 (0.1–72.5) ml] was significantly smaller than both BTVFET and BTVGE180 (p < 0.001 each), leading to a poor spatial correlation with BTVGE-180 [0.29 (0.01–0.48)] and BTVFET [0.38 (0.01–0.68)].
PET with 18F-GE-180 and 18F-FET provides differing imaging information in HGG dependent on the IDH-mutational status, with diverging spatial overlap and vast exceedance of contrast-enhancement in MRI. Combined PET imaging might reveal new insights regarding non-invasive characterization of tumour heterogeneity and might influence patients’ management.
Keywords18F-GE-180 TSPO 18F-FET Amino acid MRI High-grade glioma
We thank Dr. V. Milenkovic for the support regarding polymorphism genotyping. Additionally, we thank Joanne Stevens and GE-Healthcare for the support regarding tracer production.
Compliance with ethical standards
Conflict of interest
All authors declare that they have no relationships or interests that could have direct or potential influence or impart bias on the work.
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.
All patients gave written consent to participate in the study.
- 13.Tang D, Nickels ML, Tantawy MN, Buck JR, Manning HC. Preclinical imaging evaluation of novel TSPO-PET ligand 2-(5,7-Diethyl-2-(4-(2-[(18)F]fluoroethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)- N,N-diethylacetamide ([ (18)F]VUIIS1008) in glioma. Molec Imaging Biol. 2014;16:813–20.CrossRefGoogle Scholar
- 16.Pappata S, Cornu P, Samson Y, Prenant C, Benavides J, Scatton B, et al. PET study of carbon-11-PK 11195 binding to peripheral type benzodiazepine sites in glioblastoma: a case report. J Nucl Med. 1991;32:1608–10.Google Scholar
- 28.Suchorska B, Giese A, Biczok A, Unterrainer M, Weller M, Drexler M, et al. Identification of time-to-peak on dynamic 18F-FET-PET as a prognostic marker specifically in IDH1/2 mutant diffuse astrocytoma. Neurooncol. 2017;20(2):279–288.Google Scholar
- 38.Sørensen T. A method of establishing groups of equal amplitude in plant sociology based on similarity of species and its application to analyses of the vegetation on Danish commons. Biol Skr. 1948;5:1–34.Google Scholar
- 39.Law I, Albert NL, Arbizu J, Boellaard R, Drzezga A, Galldiks N, et al. A joint RANO/EANO/EANM Practice Guideline/SNMMI Procedure Standard for Imaging of Gliomas using PET with Radiolabeled Amino Acids and [18F]FDG: Version 1.0. SNMMI Publications. 2018.Google Scholar
- 40.Jansen NL, Schwartz C, Graute V, Eigenbrod S, Lutz J, Egensperger R, et al. Prediction of oligodendroglial histology and LOH 1p/19q using dynamic [18F] FET-PET imaging in intracranial WHO grade II and III gliomas. Neurooncol. 2012;14:1473–80.Google Scholar
- 43.Unterrainer M, Winkelmann I, Suchorska B, Giese A, Wenter V, Kreth FW, et al. Biological tumour volumes of gliomas in early and standard 20–40 min 18F-FET PET images differ according to IDH mutation status. Eur J Nucl Med Mol Imaging. 2018;45:1242–9. https://doi.org/10.1007/s00259-018-3969-4.CrossRefGoogle Scholar