Avoid common mistakes on your manuscript.
A 51-year-old female patient presented with newly onset seizure. MR imaging revealed a T2-hyperintense lesion without contrast enhancement in the right temporoinsular region showing low uptake on both amino acid PET with [18F]FET and TSPO PET with [18F]GE180. Stereotactic biopsy revealed an IDH-wildtype glioma, MGMT-methylated, with a TERT promoter mutation and a proliferation index of 10%, consistent with a WHO grade 4 glioblastoma according to the current classification [1]. After radiochemotherapy according to EORTC/NCIC protocol [2], [18F]FET uptake remained continually low, while [18F]GE180 PET showed a focally increased uptake in the treated area. The patient remained stable for a remarkably long period, until tumor recurred locally after 4.3 years. At recurrence, both [18F]FET PET and [18F]GE180 PET showed an equally strong uptake.
TSPO expression has not only been linked to malignant tumor cells [3,4,5,6], but is particularly known as an inflammation marker [7,8,9]. As such, increased [18F]GE180 uptake immediately after therapy in the absence of [18F]FET uptake might reflect treatment-related inflammation as has been described after radio- [10, 11] or chemotherapy [12]. This is the first human case demonstrating diverging amino acid and TSPO PET findings after radiochemotherapy in a glioblastoma patient with favorable treatment response. Although low initial FET uptake also indicates favorable outcome and no tissue samples are available for histological correlation immediately after therapy, it is intriguing to speculate that the distinct uptake patterns in dual tracer PET imaging might capture therapy-induced immune response, which may serve as interesting biomarker and should be evaluated in future studies.
References
Louis DN, et al. The 2021 WHO classification of tumors of the central nervous system: a summary. Neuro Oncol. 2021;23(8):1231–51.
Stupp R, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96.
Cai L, Kirchleitner SV, Zhao D, Li M, Tonn JC, Glass R, Kälin RE. Glioblastoma exhibits inter-individual heterogeneity of TSPO and LAT1 expression in neoplastic and parenchymal cells. Int J Mol Sci. 2020;21(2):612.
Unterrainer M, et al. TSPO PET, tumour grading and molecular genetics in histologically verified glioma: a correlative (18)F-GE-180 PET study. Eur J Nucl Med Mol Imaging. 2020;47(6):1368–80.
Unterrainer M, et al. Comparison of (18)F-GE-180 and dynamic (18)F-FET PET in high grade glioma: a double-tracer pilot study. Eur J Nucl Med Mol Imaging. 2019;46(3):580–90.
Albert NL, et al. TSPO PET for glioma imaging using the novel ligand (18)F-GE-180: first results in patients with glioblastoma. Eur J Nucl Med Mol Imaging. 2017;44(13):2230–8.
Unterrainer M, et al. TSPO PET with [(18)F]GE-180 sensitively detects focal neuroinflammation in patients with relapsing-remitting multiple sclerosis. Eur J Nucl Med Mol Imaging. 2018;45(8):1423–31.
Zinnhardt B, Roncaroli F, Foray C, Agushi E, Osrah B, Hugon G, Jacobs AH, Winkeler A. Imaging of the glioma microenvironment by TSPO PET. Eur J Nucl Med Mol Imaging. 2021;49(1):174–85.
Zinnhardt B, et al. TSPO imaging-guided characterization of the immunosuppressive myeloid tumor microenvironment in patients with malignant glioma. Neuro Oncol. 2020;22(7):1030–43.
Deloch L, et al. Modern radiotherapy concepts and the impact of radiation on immune activation. Front Oncol. 2016;6:141.
McLaughlin M, et al. Inflammatory microenvironment remodelling by tumour cells after radiotherapy. Nat Rev Cancer. 2020;20(4):203–17.
Foray C, et al. Imaging temozolomide-induced changes in the myeloid glioma microenvironment. Theranostics. 2021;11(5):2020–33.
Acknowledgements
N.L.A. thanks the Else Kröner-Fresenius-Stiftung for the support of her research.
Funding
Open Access funding enabled and organized by Projekt DEAL. This project was partly funded by the Deutsche Forschungsgemeinschaft (FOR 2858 project number 421887978).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent
Informed consent was obtained from all individual participants included in the study.
Conflict of interest
The authors declare no competing interests.
Additional information
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This article is part of the Topical Collection on Image of the month
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Quach, S., Holzgreve, A., von Baumgarten, L. et al. Increased TSPO PET signal after radiochemotherapy in IDH-wildtype glioma—indicator for treatment-induced immune activation?. Eur J Nucl Med Mol Imaging 49, 4282–4283 (2022). https://doi.org/10.1007/s00259-022-05844-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00259-022-05844-3