[18F]FET PET enables histopathology-validated detection of non-contrast-enhancing glioblastoma
Abstract Accurate visualization of glioblastoma is essential for guiding biopsy, resection and radiotherapy. Contrast-enhanced MRI is routine in clinical practice, yet it can miss metabolically active tumor outside areas of blood-brain barrier disruption. In a histopathology-validated cohort with 472 tissue samples of 61 patients with IDH-wildtype glioblastoma, we show that O-(2-[¹⁸F]fluoroethyl)-L-tyrosine PET ([ 18 F]FET PET) depicts tumor tissue significantly better than contrast-enhanced MRI (CE-MRI), especially in regions that show no enhancement on MRI. [ 18 F]FET PET achieves substantially higher sensitivity for tumor detection (91.2% vs 52.6%) and maintains high reliability in non-enhancing tissue (positive predictive value 98.3%), findings that are consistent across newly diagnosed and recurrent disease and in both cohorts undergoing either resection or biopsy. These results indicate that [ 18 F]FET PET complements MRI by revealing MRI-occult tumor burden. Incorporating amino acid PET into routine planning may therefore improve the accuracy of tumor visualization and, ultimately, patient management.
Authors
- Sabrina Viktoria Kirchleitner (ORCID: https://orcid.org/0000-0001-6864-3369)
- Tobias Greve (ORCID: https://orcid.org/0000-0003-2973-5687)
- Louisa von Baumgarten (ORCID: https://orcid.org/0000-0002-6634-0927)
- Nathalie L. Albert (ORCID: https://orcid.org/0000-0003-0953-7624)
- Matthias Brendel (ORCID: https://orcid.org/0000-0002-9247-2843)
- Stefanie Quach (ORCID: https://orcid.org/0000-0003-2914-3649)
- Adrian Jun Zounek (ORCID: https://orcid.org/0000-0001-8765-1276)
- Isabelle von Polenz (ORCID: https://orcid.org/0009-0002-6288-5134)
- Markus J. Riemenschneider (ORCID: https://orcid.org/0000-0002-3742-2982)
- Jörg‐Christian Tonn (ORCID: https://orcid.org/0009-0004-1756-423X)
- V. C. Ruf
- J. Lorenz (ORCID: https://orcid.org/0009-0002-4761-4643)
- K. J. Schmidbauer
- D. Kalasauskas
- R. Rupprecht
- F. Ringel
- E. Barci
- J. Blobner
- L. Kaiser
- S. Stöcklein
- R. Stürzl
- N. Thon
- P. Harter
- V. Stöcklein
Institutions
- German Cancer Research Center (DE)
- Bielefeld University (DE)
- Heidelberg University (DE)
- German Center for Neurodegenerative Diseases (DE)
- LMU Klinikum (DE)
- University Hospital Regensburg (DE)
- Universitätsklinikum Knappschaftskrankenhaus Bochum (DE)
- Munich Cluster for Systems Neurology (DE)
- Institut für Neuropathologie (DE)
- University of Regensburg (DE)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-11-06
- DOI
- https://doi.org/10.1038/s41467-026-78980-1
- Primary Topic
- Glioma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Deutsche Forschungsgemeinschaft