Comparative Insights into 18F-FDG and 68Ga-FAPI PET Imaging in Glioma: Diagnostic Value, Tumor Grading, and Clinical Implications

Gliomas are the most common primary malignant brain tumors and are characterized by heterogeneous growth and complex biology, which complicate accurate diagnosis and management. While magnetic resonance imaging (MRI) remains the clinical standard, its limitations in delineating tumor margins and distinguishing recurrence from treatment-induced changes highlight the need for complementary molecular imaging. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) has been extensively studied, providing valuable prognostic information by reflecting tumor glycolytic activity. However, its diagnostic utility is hampered by high cortical background uptake and by poor sensitivity in detecting low-grade gliomas. Conversely, glioma-68 fibroblast activation protein inhibitor (FAPI) PET targets cancer-associated fibroblasts, offering superior tumor-to-background contrast and improved visualization of infiltrative margins. Comparative studies suggest that FAPI PET better discriminates between low- and high-grade gliomas, correlates with tumor stromal activity, and aids in therapy planning by differentiating true progression from post-treatment changes. Despite these advantages, the evidence base for FAPI remains limited, largely derived from small cohorts and pilot studies. Standardized imaging protocols and larger prospective trials are necessary to validate its role. Overall, 18F-FDG and FAPI PET provide complementary insights into glioma biology, and their integration with MRI and amino acid tracers may refine diagnostic accuracy, therapeutic planning, and prognostic assessment in clinical neuro-oncology.