[18F]DOPA PET identifies metabolically active tumor beyond contrast-enhancing margins in IDH-WT glioblastoma: a histopathology and fluorescence validation study
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ID: 320113
2026
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Abstract
Abstract Background Supramaximal resection in IDH-wildtype glioblastoma (GB) improves survival, yet identifying tumor infiltration within FLAIR-hyperintense peritumoral areas remains challenging. This study aims to validate the use of [¹⁸F]DOPA PET for identifying metabolically active tumor beyond Contrast enhancing (CE) margins, correlating imaging with histopathology and intraoperative fluorescence. Methods Patients with newly diagnosed IDH-wt GB scheduled for supramaximal resection and undergoing preoperative DOPA-PET and MRI were prospectively enrolled from the ResPGlioma study. The Biological Tumor Volume (BTV) was semi-automatically delineated using the contralateral striatal SUVmean as the PET positivity threshold. Before resection, biopsy samples were collected from five radiologically distinct areas: CE, FLAIR+PET (FP), PET-only (Po), FLAIR-only (Fo), and normal tissue (N). Each sample was blindly assessed for neoplastic, necrotic, and infiltrative components, mitotic count, microvascular proliferation. Intraoperative 5-aminolevulinic acid (5-ALA) and fluorescein sodium (FS) uptake were also recorded. Results Twenty-five samples from 5 patients were analyzed. The BTV, defined using a striatal SUVmean threshold, extended beyond CE-MRI margins in 100% of cases (mean BTV 30.4 ± 17.6 cm³ vs. mean CE volume 20.6 ± 16.9 cm³). PET-positive areas (FLAIR+/PET+ and PET-only) showed significantly higher neoplastic cell density and mitotic counts compared to FLAIR-only (P < .005) and normal areas (P < .005). No significant histopathological differences were found between PET-only and CE regions, whereas FLAIR-only samples primarily exhibited white matter infiltration and reactive changes. Uptake of 5-ALA and SF was significantly more intense and frequent in PET-positive areas (CE, FP, Po) compared to Fo and N areas (P = .015 and P < .001, respectively). Conclusions This preliminary study provides histopathological and fluorescence validation that [¹⁸F]DOPA PET identifies areas of high tumor burden within the peritumoral zone, comparable to the contrast-enhancing core. The integration of amino acid PET in preoperative planning should be considered to guide targeted supramaximal resection of metabolic hotspots in IDH-wildtype glioblastoma.
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| Authors | Andrea Bianconi, Alessandro Pesaresi, Raffaele De Marco, Michela Zotta, Luca Bertero, Francesco Bruno, Edoardo Pronello, Giulia Capella, Flavio Panico, Adriana Lesca, Fabio Cofano, Paola Cassoni, Giovanni Morana, Roberta Rudà, Silvia Morbelli, Diego Garbossa |
| Journal | Neuro-Oncology Practice |
| Year | 2026 |
| DOI |
10.1093/nop/npag065
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| URL | |
| Keywords | Keywords not found |
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