Association of tumor metabolic parameters on amino acid PET/CT with EGFR expression
Журнал: Вопросы нейрохирургии имени Н.Н. Бурденко. 2026;90(5):39-45.
DOI: 10.17116/neiro20269005139
Read: 644 раза
Abstract
BACKGROUND
According to the 2021 WHO classification, molecular-genetic profiling of CNS tumors is the standard for diagnosis. Beyond IDH mutation status, EGFR receptor alterations are significant factors associated with unfavorable prognosis and treatment resistance. Identifying correlations between genetic abnormalities and amino acid PET/CT parameters is important for discovering non-invasive surrogate markers of aggressive phenotype.
OBJECTIVE
To analyze the relationship between EGFR / EGFRvIII gene expression and metabolic PET/CT parameters in patients with glial tumors.
MATERIAL AND METHODS
The study included 71 adults with gliomas: glioblastoma (n=52), Grade 3 astrocytoma (n=11), and Grade 3 oligodendroglioma (n=8). All patients underwent PET/CT with ¹¹C-MET (n=41) or ¹8F-FET (n=30). The tumor-to-background ratio (TBR) and metabolic tumor volume (MTV) were calculated using a TBR segmentation threshold of 1.6. EGFR / EGFRvIII expression was determined via RT-PCR.
RESULTS
EGFR expression was significantly higher in glioblastomas compared to astrocytomas and oligodendrogliomas. A significant positive correlation was found between EGFR and MTV (Rs=0.44, p=0.02). In patients with astrocytomas, there was a moderate negative correlation between TBR and EGFR expression (Rs=–0.64, p=0.04). No significant correlations were observed in glioblastomas and oligodendrogliomas that may be attributed to high variability of EGFR. EGFRvIII was expressed in 25% of gliomas (exclusively glioblastomas). However, we found no association with metabolic parameters (possibly due to small sample size).
CONCLUSION
Differences in EGFR expression patterns across various glioma types were demonstrated. Correlation between EGFR gene expression and tumor metabolic volume suggests potential role for PET/CT parameters as prognostic markers.
Keywords
- PET/CT
- gliomas
- EGFR expression
- EGFRvIII
Дата поступления: 19.05.2026
Дата принятия в печать: 01.09.2026
Дата публикации: 16.10.2026
- Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, Hawkins C, Ng HK, Pfister SM, Reifenberger G, Soffietti R, Von Deimling A, Ellison DW. The 2021 WHO classification of tumors of the central nervous system: A summary. Neuro-Oncology. 2021;23(8):1231-1251. https://doi.org/10.1093/neuonc/noab106
- Lerner A, Palmer K, Campion T, Millner TO, Scott E, Lorimer C, Paraskevopoulos D, McKenna G, Marino S, Lewis R, Plowman N. Gliomas in adults: Guidance on investigations, diagnosis, treatment and urveillance. Clinical Medicine. 2024;24(5):100240. https://doi.org/10.1016/j.clinme.2024.100240
- Rodriguez SMB, Kamel A, Ciubotaru GV, Onose G, Sevastre A-S, Sfredel V, Danoiu S, Dricu A, Tataranu LG. An Overview of EGFR Mechanisms and Their Implications in Targeted Therapies for Glioblastoma. International Journal of Molecular Sciences. 2023; 24(13):11110. https://doi.org/10.3390/ijms241311110
- Begagić E, Pugonja R, Bečulić H, Čeliković A, Tandir Lihić L, Kadić Vukas S, Čejvan L, Skomorac R, Selimović E, Jaganjac B, et al. Molecular Targeted Therapies in Glioblastoma Multiforme: A Systematic Overview of Global Trends and Findings. Brain Sciences. 2023; 13(11):1602. https://doi.org/10.3390/brainsci13111602
- Shah S, Nag A, Sachithanandam SV, Lucke-Wold B. Predictive and Prognostic Significance of Molecular Biomarkers in Glioblastoma. Biomedicines. 2024; 12(12):2664. https://doi.org/10.3390/biomedicines12122664
- Nikitin PV, Ryzhova MV, Potapov AA, Galstyan SA, Kim DS, Panina TN, Shugai SV, Starovoitov DV, Khokhlova EA, Zubova IV. Glioblastoma molecular and histological heterogeneity. Clinical and Experimental Morphology. 2020;9(3):5-11. (In Russ.). https://doi.org/10.31088/CEM2020.9.3.5-11
- S S, Galldiks N, Lohmann P, Friedrich M, Werner JM, Stetter I, Wollring MM, Ceccon G, Stegmayr C, Krause S, Fink GR, Law I. Neuro-Oncology PET imaging of gliomas: Status quo and quo vadis? Neuro-Oncology. 2024;26:185-198. https://doi.org/10.1093/neuonc/noae078
- Vikhrova NB, Kalaeva DB, Tyurina AN, Belyaev AYu, Danilov GV, Pronin IN. PET/CT with 11C-methionine in assessment of brain glioma metabolism. Burdenko’s Journal of Neurosurgery. 2024;88(1):63-69. (In Russ., In Engl.). https://doi.org/10.17116/neiro20248801163
- Danilov G, Postnov A, Kobyakova T, Pronin I. Can Radiomics of Dynamic PET Imaging with 11C-methionine Predict EGFR Amplification Status in Glioblastoma? Applied Medical Informatics. 2024;46:1-4.
- Bai J, Cui B, Li F, Ha X, Yang H, Lu J. Multiparametric radiomics signature for predicting molecular genotypes in adult-type diffuse gliomas utilizing 18F-FET PET/MRI. BMC Med Imaging. 2025;25:187. https://doi.org/10.1186/s12880-025-01729-7
- Vikhrova N, Kalaeva D, Batalov A, Pronin I. Phenotypic and genetic heterogeneity of glioblastomas: comparison of MRI and PET/CT parameters with molecular genetic characteristics of the tumor. I.P. Pavlov Journal of Higher Nervous Activity. 2024; 74(1):48-59. (In Russ.). https://doi.org/10.31857/S0044467724010051
- Mair MJ, Werner JM, Weller J et al. Prognostic stratification of newly diagnosed IDH-mutant gliomas by [18F]fluoroethyltyrosine and [11C]methionine PET — a retrospective, bicentric cohort study. Neuro-Oncology. 2025;27(12):3292-3305. https://doi.org/10.1093/neuonc/noaf196
- Vikhrova NB, Kalaeva DB, Postnov AA, Khokhlova EV, Konakova TA, Batalov AI, Pogosbekyan EL, Pronin IN. Dynamic 11C-methionine PET/CT in differential diagnosis of brain gliomas. Burdenko’s Journal of Neurosergery. 2021;85(3):5-11. (In Russ., In Engl.). https://doi.org/10.17116/neiro2021850315
- Bhusare N, Kumar M. A review on potential heterocycles for the treatment of glioblastoma targeting receptor tyrosine kinases. Oncology Research. 2024;32(5):849-875. https://doi.org/10.32604/or.2024.047042
- Zhu F, Qiu J, Ye H, Su W, Wang R. The Prognostic Significance of Epidermal Growth Factor Receptor Amplification and Epidermal Growth Factor Receptor Variant III Mutation in Glioblastoma: A Systematic Review and Meta-Analysis with Implications for Targeted Therapy. International journal of molecular sciences. 2025;26(8):3539. https://doi.org/10.3390/ijms26083539
- Wang H, Zhang X, Liu J, Chen W, Guo X, Wang Y, Wang Y, Xing H, Liang T, Shi Y, Liu D, Yang T, Xia Y, Li J, Wu J, Liu Q, Qu T, Guo S, Li H, Zhang K, Li Y, Jin S, Zhao D, Wang Y, Ma W. Clinical roles of EGFR amplification in diffuse gliomas: a real-world study using the 2021 WHO classification of CNS tumors. Frontiers in Neuroscience. 2024;18:1308627. https://doi.org/10.3389/fnins.2024.1308627
- Srivastava S, Anbiaee R, Houshyari M, Laxmi, Sridhar SB, Ashique S, Hussain S, Kumar S, Taj T, Akbarnejad Z, Taghizadeh-Hesary F. Amino acid metabolism in glioblastoma pathogenesis, immune evasion, and treatment resistance. Cancer Cell International. 2025;25(1):89. https://doi.org/10.1186/s12935-025-03721-1
- van Dijken BRJ, Ankrah AO, Stormezand GN, Dierckx RAJO, van Laar PJ, van der Hoorn A. Prognostic value of 11C-methionine volume-based PET parameters in IDH wild type glioblastoma. PLoS ONE. 2022;17(2): e0264387. https://doi.org/10.1371/journal.pone.0264387
- Dadgar H, Jokar N, Nemati R, Larvie M, Assadi M. PET tracers in glioblastoma: Toward neurotheranostics as an individualized medicine approach. Frontiers in Nuclear Medicine. 2023;3:1103262. https://doi.org/10.3389/fnume.2023.1103262
- Belyaev AYu, Vikhrova NB, Kalaeva DB, Batalov AI, Afandiev RM, Galstyan SA, Kobyakov GL, Pronin IN, Usachev D. PET-CT with 11C-methionine in the diagnosis of anaplastic astrocytomas and anaplastic oligodendrogliomas. Meditsinskaya vizualizatsiya. 2022;0763:82-92. (In Russ.).
- Yuan F, Wang Y, Yuan L, Tang T, Ye L, Li Y, Dai X, Cheng H. EGFRvIII-positive glioblastoma contributes to immune escape and malignant progression via the c-Fos-MDK-LRP1 axis. Cell Death & Disease. 2025;16(1):1-16. https://doi.org/10.1038/s41419-025-07771-1
- Cetin MH, Rieckmann T, Hoffer K, Riepen B, Christiansen S, Gatzemeier F, Feyerabend S, Schoof M, Schüller U, Petersen C, Mynarek M, Rothkamm K, Kriegs M, Struve N. G2 checkpoint targeting via Wee1 inhibition radiosensitizes EGFRvIII-positive glioblastoma cells. Radiation Oncology (London, England). 2023;18(1):19. https://doi.org/10.1186/s13014-023-02210-x
- Zhu F, Qiu J, Ye H, Su W, Wang R, Fu Y. The Prognostic Significance of Epidermal Growth Factor Receptor Amplification and Epidermal Growth Factor Receptor Variant III Mutation in Glioblastoma: A Systematic Review and Meta-Analysis with Implications for Targeted Therapy. International Journal of Molecular Sciences. 2025; 26(8):3539. https://doi.org/10.3390/ijms26083539
- Piscopo L, Zampella E, Klain M. [18F]FET PET/MR and machine learning in the evaluation of glioma. European Journal of Nuclear Medicine and Molecular Imaging. 2024;51(3):797-799. https://doi.org/10.1007/s00259-023-06505-9
- Galkin MV, Vikhrova NB, Golanov AV, Danilov GV, Strunina YV. C-Methionine PET/CT in Meningioma. Neuroscience and Behavioral Physiology. 2024;54(6):894-899. https://doi.org/10.1007/s11055-024-01673-z
Recommended articles:
IDH-mutant gliomas. State of the art.Burdenko's Journal of Neurosurgery. 2026;90(5):70-75
Diagnostic value of bone marrow biopsy in primary extranodal non-Hodgkin lymphomas: a comparative analysis of trephine biopsy, myelogram, and PET/CT.P.A. Herzen Journal of Oncology. 2026;15(4):42-47
A «Trojan horse» for glioblastoma: targeted aptamer delivery strategy.Burdenko's Journal of Neurosurgery. 2025;89(6-2):50-56
Machine learning models for brain tumors differential diagnosis.Russian Journal of Preventive Medicine. 2025;28(9):87-93
Radionuclide methods in analysis of myocardial perfusion and metabolic activity.Regenerative Biotechnologies, Preventive, Digital and Predictive Medicine. 2024;1(4):12-19
Magnetic resonance imaging and PET/CT with 11C-methionine for primary central nervous system vasculitis.Burdenko's Journal of Neurosurgery. 2024;88(6):71-76
PET/CT with 11C-methionine as a predictor of disease-free survival in patients with IDH1 wild type diffuse glioma.Burdenko's Journal of Neurosurgery. 2024;88(5):6-13