Work

Reconstruction matters: influence of EARL standards and BSREM in [18F]FET PET for distinguishing glioma progression from treatment-related changes

Year: 2026

Type: article

Abstract: Background Differentiating progressive disease (PD) from treatment-related changes (TRC) in glioma remains challenging using magnetic resonance imaging (MRI) alone. Amino acid positron-emission tomography (PET) with O-(2-[ 18 F]fluoroethyl)-L-tyrosine ([¹⁸F]FET) is increasingly applied in clinical practice, and the first PET-Response Assessment in Neuro-Oncology (RANO) guideline has recently been developed. However, quantitative PET metrics are sensitive to image reconstruction, which may directly affect response classification and clinical interpretation. This study aimed to investigate how different reconstruction standards influence quantitative [¹⁸F]FET PET metrics and to what extent these differences may impact clinical interpretation. Results Thirty-three patients with 42 lesions were analysed. In lesion‑based comparisons, both EANM Research Ltd. harmonization standard version 2.0 (EARL2) and block-sequential regularized expectation maximization using a β-value of 150 (BSREM150) reconstructions yielded significantly higher standardized uptake values, tumour‑to‑background ratios (TBR), and biological tumour volumes (BTV) than EANM Research Ltd. harmonization standard version 1.0 (EARL1), and they identified a greater number of lesions as measurable disease (MD). BTV differed across reconstructions; it was found that adapting the BSREM150 segmentation threshold to SUV ≥ 1.7 x mean background uptake, could improve BTV concordance while maintaining superior MD detection. Excellent discrimination between progressive disease (PD) and treatment‑related changes (TRC) was found for TBRmax across all reconstructions (area under the curve ≥ 0.93), although optimal thresholds were reconstruction‑specific (EARL1: 1.67; EARL2: 1.84; BSREM150: 2.39). At the patient level, EARL1 failed to identify three PD cases, whereas BSREM150 misclassified one TRC case as PD. Conclusion Reconstruction standards substantially influence quantitative [¹⁸F]FET PET metrics and clinical interpretation. Applying universal thresholds across reconstructions risks misclassification, with EARL1 potentially underestimating tumour extent and BSREM150 increasing false-positive findings. Reconstruction-specific thresholds and neuro-oncology-specific harmonization frameworks are essential for reliable [ 18 F]FET assessment in routine clinical practice and PET-RANO implementation in multicentre trials.

Source: EJNMMI Research

DOI: 10.1186/s13550-026-01458-0