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Diagnostic and Prognostic Value of Hypoxia PET in Glioma: A Systematic Review and Meta-Analysis
Aly Muhammad Ladak1, Seyed Ali Mirshahvalad1,2, Adam Farag1
1University Medical Imaging Toronto, Joint Department of Medical Imaging, University Health Network, Sinai Health System & Women's College Hospital, Toronto, ON M5G 2N2, Canada.
Abstract:
Background/Objectives: While MRI is effective for glioma diagnosis, it has limitations in grading, treatment planning, and prognostication. Since hypoxia is associated with higher-grade gliomas and poorer outcomes, PET imaging with hypoxia-specific tracers has been shown to improve glioma assessment. This systematic review and meta-analysis aimed to evaluate the performance of hypoxia PET imaging in glioma diagnosis and prognostication. Methods: Systematic searches were conducted across PubMed, Web of Science, and Scopus through 31 January 2025. Only studies assessing the diagnostic or prognostic value of PET with 18F-labelled nitroimidazole (18F-FMISO, 18F-FAZA, 18F-FRP170, or 18F-FETNIM) or 62Cu-labelled ATSM hypoxia tracers in patients with gliomas were included. Hierarchical models were used to evaluate pooled performance on differentiating glioblastoma from lower-grade gliomas. Results: Thirty-eight articles (n = 1156 patients) were eligible for inclusion, and eleven articles (n = 296 patients) were suitable for meta-analytical calculations. The extent of hypoxia on PET imaging was generally correlated with isocitrate dehydrogenase (IDH) mutation status and histological angiogenesis. Hypoxia PET was effective at differentiating glioblastoma from lower-grade gliomas and at predicting overall and progression-free survival. In a pooled analysis, 18F-FMISO PET displayed high sensitivity (98%) and specificity (94%) for differentiating glioblastoma from lower-grade gliomas. Conclusions: Hypoxia PET has the potential to predict tumour biology, and it may be a reliable modality in combination with MRI to provide complementary information for glioma diagnosis, grading, treatment planning, and prognostication. It may be particularly useful for ruling out glioblastoma in patients with otherwise equivocal imaging; however, this would need to be validated prospectively with standardized image acquisition and interpretation criteria.
Insights
Hypoxia PET imaging shows promise for glioma diagnosis and prognostication, accurately differentiating glioblastoma from lower-grade gliomas and predicting patient survival. This technique offers valuable complementary information to MRI for improved glioma assessment.
Area of Science:
- Oncology
- Radiology
- Nuclear Medicine
Background:
- Magnetic Resonance Imaging (MRI) has limitations in accurately grading, planning treatment for, and predicting outcomes in glioma patients.
- Tumor hypoxia is linked to higher-grade gliomas and poorer prognoses, making hypoxia-specific positron emission tomography (PET) tracers valuable for improved assessment.
- This systematic review and meta-analysis evaluates the diagnostic and prognostic performance of hypoxia PET imaging in gliomas.
Purpose of the Study:
- To systematically review and meta-analyze the performance of hypoxia PET imaging in glioma diagnosis.
- To evaluate the prognostic value of hypoxia PET imaging for glioma patients.
- To assess the utility of PET tracers like 18F-labelled nitroimidazoles and 62Cu-labelled ATSM in differentiating glioma grades and predicting survival.
Main Methods:
- Systematic literature searches were performed in PubMed, Web of Science, and Scopus up to January 31, 2025.
- Studies included assessed the diagnostic or prognostic value of specific hypoxia PET tracers (18F-FMISO, 18F-FAZA, 18F-FRP170, 18F-FETNIM, 62Cu-ATSM) in glioma patients.
- Hierarchical models were employed for pooled performance analysis, particularly for differentiating glioblastoma from lower-grade gliomas.
Main Results:
- Thirty-eight articles (1156 patients) were eligible, with eleven (296 patients) included in meta-analyses.
- Hypoxia extent on PET correlated with IDH mutation status and histological angiogenesis.
- Hypoxia PET demonstrated high sensitivity (98%) and specificity (94%) for differentiating glioblastoma from lower-grade gliomas using 18F-FMISO, and effectively predicted overall and progression-free survival.
Conclusions:
- Hypoxia PET imaging shows potential for predicting tumor biology and serves as a reliable tool complementary to MRI for glioma diagnosis, grading, and prognostication.
- This modality may be particularly useful for ruling out glioblastoma in cases with equivocal MRI findings.
- Prospective validation with standardized imaging protocols is recommended to confirm these findings.
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