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. 2025 Aug 28.
doi: 10.1007/s00259-025-07520-8. Online ahead of print.

Spatial tumour characteristics as an indirect marker of metabolic dysregulation: evaluation for non-invasive IDH-genotyping of glioma using hybrid [18 F]FET-PET/MRI

Johannes Lohmeier  1 , Jenny Meinhardt  2 , Helena Radbruch  2 , Mauricio Reyes  3   4 , Winfried Brenner  5 , Anna Tietze  6 , Marcus R Makowski  7
Affiliations

Spatial tumour characteristics as an indirect marker of metabolic dysregulation: evaluation for non-invasive IDH-genotyping of glioma using hybrid [18 F]FET-PET/MRI

Johannes Lohmeier et al. Eur J Nucl Med Mol Imaging. .

Abstract

Purpose: The isocitrate dehydrogenase (IDH) genotype is crucial for diagnosing and managing adult-type diffuse glioma. We investigated spatial tumour characteristics in treatment-naïve glioma using an U-Net-based CNN and evaluated associations with metabolic dysfunction and IDH genotype.

Methods: Between 2015 and 2024 patients with confirmed contrast-enhancing glioma were pre-operatively investigated using MRI or [18 F]FET PET/MRI. Automated morphometry using a U-Net-based CNN on standard MRI sequences (T1c, T1, T2, FLAIR) was performed. Contrast-enhancing tumour fraction (CTF), metabolic tumour volume (MTV), total tumour volume (TTV) were determined. Dice coefficient assessed volume intersections. Comparative and statistical analyses included non-parametric tests, ROC curves, regression, and correlation.

Results: A total of 180 patients (male, 114; female, 66; age, M ± SD = 54 ± 15y; IDH-mutant, 63; IDH wild-type, 117) with treatment-naïve glioma were evaluated. [18 F]FET-PET metabolic activity correlated significantly with CTF (p < .05). IDH-mutant gliomas had lower CTF (p < .001) due to higher non-enhancing tumour mass (p < .001) relative to the enhancing mass, unlike IDH wild-type glioblastoma. The CTF predicted IDH genotype with high accuracy (AUC = 0.85, sensitivity 78%, specificity 90%) across datasets. Combining CTF with patient age or SUVmax further improved the classification (ΔAUC = 0.12, p = .02; ΔAUC = 0.09, p > .05). Subgroup analyses showed consistent performance across IDH-mutant subtypes. MTV from [18 F]FET-PET exceeded structurally apparent TTV (p = .033).

Conclusion: Spatial mapping of treatment-naïve glioma identified a non-invasive biomarker, which is linked to metabolic dysfunction and enabled robust IDH-genotype classification from standard MRI, suggesting a central role for radiogenomic assessment in adult-type diffuse gliomas prior to surgery.

Keywords: Neuro-oncology; PET/MRI; Predictive IDH-genotyping; Radiogenomic biomarker; Spatial phenotyping; Spatial tumour characteristics.

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Conflict of interest statement

Declarations. Ethics approval: This retrospective clinical cohort study was conducted according to the principles of the Helsinki Declaration and approval from the institutional ethics board (EA2/019/23) was obtained. Informed consent was obtained from all individual participants included in the study. The authors affirm that human research participants provided informed consent for publication of the images. Competing interests: The authors declare no competing interests. Clinical trial number: Not applicable.

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